HETEROCYCLIC COMPOUNDS AND USES THEREOF CROSS-REFERENCE [0001] This application claims the benefit of U.S. Provisional Patent Application Nos.63/301,474 filed on January 20, 2022, 63/328,183 filed on April 6, 2022, and 63/338,386 filed on May 4, 2022, each of which is incorporated by reference in its entirety. BACKGROUND [0002] Cancer (e.g., tumor, neoplasm, metastases) is the second leading cause of death worldwide estimated to be responsible for about 10 million deaths each year. Many types of cancers are marked with mutations in one or more proteins involved in various signaling pathways leading to unregulated growth of cancerous cells. In some cases, about 25 to 30 percent (%) of tumors are known to harbor Rat sarcoma (Ras) mutations. Ras proteins such as human H-Ras, K-Ras, and N-Ras are small GTPase proteins involved in signal transduction pathways that regulate diverse cellular behaviors. When Ras proteins are activated or switched on by upstream signals, they in turn activate downstream components of signal transductions pathways, culminating in dysregulated cellular activities responsible for abnormal cell growth, differentiation, and/or survival. [0003] Various types of Ras mutations have been found to associate with a variety of cancers. For example, K-Ras mutations have been found in lung cancer (e.g., lung adenocarcinoma), mucinous adenoma, pancreatic cancer (e.g., ductal carcinoma of the pancreas), colorectal cancer, and leukemia. Mutation and dysregulation of the function of N-Ras are associated with different lung cancers and melanoma. H-Ras mutations have been found associated with head and neck cancer and other types of cancer as well. [0004] Ras proteins have long been considered “undruggable,” due to, in part, high affinity to their substrate guanosine-5'-triphosphate (GTP) and/or their smooth surfaces without any obvious targeting region. A specific G12C Ras gene mutation has been identified as a druggable target to which a number of G12C specific inhibitors have been developed. However, such therapeutics are still of limited application as the G12C mutation in Ras exhibits a much lower prevalence rate as compared to other known Ras mutations including G12D and G12V. SUMMARY [0005] In view of the foregoing, there remains a considerable need for a new design of therapeutics and diagnostics that can specifically target Ras mutants and/or associated proteins of Ras to reduce Ras signaling output. Of particular interest are inhibitors of mutant Ras proteins such as Ras G12D, G12C, G12S, G13D, and/or G12V, for the treatment of Ras-associated diseases (e.g., cancer). Such compositions and methods can be particularly useful for treating a variety of the diseases including, but not limited to, cancers and neoplasia conditions. The present disclosure addresses these needs, and provides additional advantages applicable for diagnosis, prognosis, and/or treatment for a wide diversity of diseases. [0006] In an aspect is provided a compound of Formula (I-5), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-5); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ); each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ - C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, - CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1- 11heterocycloalkyl, C _6- 12aryl, -CH ₂ -C _6- 12aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6- 12aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1- 6alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently selected from , , ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _{2- 11} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _{1- 6} alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; ^{each R20a, R20b, R20c, R20d, R20e, R20f, R20g, R20h, and R20i are each independently selected from halogen, oxo, -CN,} C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [0007] In an aspect is provided a compound of Formula (I-6), or a pharmaceutically acceptable salt or solvate thereof: W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ); each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a W ^5b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1- 6alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, - CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3- 12cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _{1- 11} heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 3-5 membered heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; ^e ach R4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C ₂ - 11heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _{1- 6} alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; wherein the compound is capable of covalently modifying a Ras protein; and indicates a single or double bond such that all valences are satisfied. [0008] In an aspect is provided a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: W ¹ is N, N(R ^1b ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1b ) each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ) each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ^5a and W ^5b are independently a bond, -NR ^5b -, -N=, -CR ⁵ =, -CR ⁵ R ^5a -, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3- 12cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _{3- 12} cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1- 6alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 3-5 membered heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C ₂ - 1 ₁ heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [0009] In some embodiments, L ¹¹ is selected from a bond, -O-, -NH-, -NCH ₃ -, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -S ⁺ (O-)-, -P(O)CH ₃ -, and -CH ₂ -. [0010] In some embodiments, L ¹¹ is selected from a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -S ⁺ (O-)-, -P(O)CH ₃ -, and -CH ₂ -. [0011] In some embodiments, R ¹¹ is a 3-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [0012] In some embodiments, R ¹¹ is a C _6-10 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [0013] In some embodiments, R ¹¹ is a 5-10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [0014] In some embodiments, L ⁴ is selected from a bond, -C(O)-, -NHC(O)-, and-C(O)NH-. [0015] In some embodiments, R ^4b is independently selected from halogen, oxo, -CN, C _1-3 alkyl, C _3-4 cycloalkyl, C _{2- 3} heterocycloalkyl, phenyl, C _1-4 heteroaryl, -OH, -SH, -NH ₂ , -C(O)OCH ₃ , -OC(O)NH ₂ , -C(O)CH ₃ , -S(O)CH ₃ , - OC(O)CH ₃ , -C(O)NH ₂ , -NHC(O)CH ₃ , -S(O) ₂ CH ₃ , and -S(O) ₂ NH ₂ , wherein C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _{3- 4} cycloalkyl, C _2-3 heterocycloalkyl, phenyl, and C _1-4 heteroaryl are optionally substituted with one or more R ^20h . [0016] In some embodiments, R ¹⁷ is selected from: Q ³ is N or C(R ^1d ); Q ⁴ is O or S; X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . [0017] In some embodiments, R ¹⁷ is ¹⁷ . In some embodiments, R is In some embodiments, R ¹⁷ is . In some embodiments, R ¹⁷ is In some embodiments, R ¹⁷ is In some embodiments, R ¹⁷ is . [0018] In some embodiments, R ¹⁷ is selected from:

[0019] In some embodiments, W ² is CR ² or CH(R ² ). In some embodiments, W ² is C(R ² ). In some embodiments, W ² is C(O). In some embodiments, W ² is N. In some embodiments, W ² is N(R ^2b ). In some embodiments, W ² is C(R ² ) ₂ . In some embodiments, W ² is C(S). In some embodiments, W ² is C(=NR ^2b ). [0020] In some embodiments, R ² is selected from , , ,

[0021] In some embodiments, the compound of Formula (I), (I-5), or (I-6) i s . In some embodiments, the compound of Formula (I), (I-5), or (I-6) is . In some embodiments, the compound of Formula (I), (I-5), or (I-6) is In some embodiments, the compound of Formula (I), (I-5), or (I-6) i In some embodiments, the compound of Formula (I), (I-5), or (I-6) is . In some embodiments, the compound of Formula (I), (I-5), or (I-6) is [0022] In some embodiments, W ¹ is N. In some embodiments, W ¹ is N(R ^1b ). In some embodiments, W ¹ is C(R ¹ ). In some embodiments, W ¹ is C(R ¹ ) ₂ . In some embodiments, W ¹ is C(O). In some embodiments, W ¹ is C(S). In some embodiments, W ¹ is C(=NR ^1b ). [0023] In some embodiments, W ³ is N. In some embodiments, W ³ is NR ^3b . In some embodiments, W ³ is CR ³ . In some embodiments, W ³ is C(R ³ )(R ^3a ). In some embodiments, W ³ is C(O). [0024] In some embodiments, W ^5a is a bond. In some embodiments, W ^5a is N. In some embodiments, W ^5a is N(R ^5b ). In some embodiments, W ^5a is C(R ⁵ ). In some embodiments, W ^5a is C(R ⁵ )(R ^5a ). In some embodiments, W ^5a is C(O). In some embodiments, W ^5a is S(O). In some embodiments, W ^5a is S(O) ₂ . In some embodiments, W ^5a is C(S). In some embodiments, W ^5a is C(NR ^5b ). In some embodiments, W ^5b is a bond. In some embodiments, W ^5b is N. In some embodiments, W ^5b is N(R ^5b ). In some embodiments, W ^5b is C(R ⁵ ). In some embodiments, W ^5b is C(R ⁵ )(R ^5a ). In some embodiments, W ^5b is C(O). In some embodiments, W ^5b is S(O). In some embodiments, W ^5b is S(O) ₂ . In some embodiments, W ^5b is C(S). In some embodiments, W ^5b is C(=NR ^5b ). [0025] In some embodiments, W ⁶ is N. In some embodiments, W ⁶ is N(R ^6b ). In some embodiments, W ⁶ is C(R ⁶ ). In some embodiments, W ⁶ is C(R ⁶ )(R ^6a ). In some embodiments, W ⁶ is C(O). In some embodiments, W ⁶ is S(O). In some embodiments, W ⁶ is S(O) ₂ . In some embodiments, W ⁶ is C(S). In some embodiments, W ⁶ is C(=NR ^6b ). [0026] In some embodiments, W ⁷ is N(R ⁷ ). In some embodiments, W ⁷ is C(R ⁷ ). In some embodiments, W ⁷ is C(R ⁷ )(R ^7a ). [0027] In some embodiments, W ⁸ is N. In some embodiments, W ⁸ is N(R ^8b ). In some embodiments, W ⁸ is C(R ⁸ ). In some embodiments, W ⁸ is C(R ⁸ )(R ^8a ). In some embodiments, W ⁸ is C(O). In some embodiments, W ⁸ is S(O). In some embodiments, W ⁸ is S(O) ₂ . In some embodiments, W ⁸ is C(S). In some embodiments, W ⁸ is C(NR ^8b ). [0028] In some embodiments, W ⁹ is C(R ¹² ). In some embodiments, W ⁹ is C. In some embodiments, W ⁹ is N. In some embodiments, W ⁹ is CH. [0029] In some embodiments, W ¹⁰ is C(R ¹² ). In some embodiments, W ¹⁰ is C. In some embodiments, W ¹⁰ is N. In some embodiments, W ¹⁰ is CH. [0030] In an aspect is provided a compound having the formula A-L ^AB -B wherein A is a monovalent form of a compound described herein; L ^AB is a covalent linker bonded to A and B; and B is a monovalent form of a degradation enhancer. [0031] In some embodiments, the degradation enhancer is capable of binding a protein selected from E3A, mdm2, APC, EDD1, SOCS/BC-box/eloBC/CUL5/RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von- Hippel-Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MKRN1, CMA (chaperon-mediated autophage), SCFb- TRCP (Skip-Cullin-F box (Beta-TRCP) ubiquitin complex), b-TRCP (b-transducing repeat-containing protein), cIAP1 (cellular inhibitor of apoptosis protein 1), APC/C (anaphase-promoting complex/cyclosome), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4 ^CRBN ) ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885. [0032] In some embodiments, the degradation enhancer is capable of binding a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1. [0033] In some embodiments, L ^AB is -L ^AB1 -L ^AB2 -L ^AB3 -L ^AB4 -L ^AB5 -; L ^AB1 , L ^AB2 , L ^AB3 , L ^AB4 , and L ^AB5 are independently a bond, -O-, -N(R ¹⁴ )-, -C(O)-, -N(R ¹⁴ )C(O)-, -C(O)N(R ¹⁴ )-, -S-, - S(O) ₂ -, -S(O)-, -S(O) ₂ N(R ¹⁴ )-, -S(O)N(R ¹⁴ )-, -N(R ¹⁴ )S(O)-, -N(R ¹⁴ )S(O) ₂ -, C _1-6 alkylene, (-O-C _1-6 alkyl) _z -, (-C _{1- 6} alkyl-O) _z -, C _2-6 alkenylene, C _2-6 alkynylene, C _1-6 haloalkylene, C _3-12 cycloalkylene, C _1-11 heterocycloalkylene, C _6- 12arylene, or C _1-11 heteroarylene, wherein C _1-6 alkylene, C _2-6 alkenylene, C _2-6 alkynylene, C _1-6 haloalkylene, C _{3- 12} cycloalkylene, C _1-11 heterocycloalkylene, C _6-12 arylene, or C _1-11 heteroarylene,are optionally substituted with one, two, or three R ^20j ; wherein each C _1-6 alkyl of (-O-C _1-6 alkyl) _z - and (-C _1-6 alkyl-O) _z - is optionally substituted with one, two, or three R ^20j ; z is independently an integer from 0 to 10; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20d , R ^20e , R ^20f , and R ^20j are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, - CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; and each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl. [0034] In some embodiments, L ^AB is -(O-C ₂ alkyl) _z - and z is an integer from 1 to 10. [0035] In some embodiments, L ^AB is -(C ₂ alkyl-O-) _z - and z is an integer from 1 to 10. [0036] In some embodiments, L ^AB is -(CH ₂ ) _zz1 L ^AB2 (CH ₂ O) _zz2 -, wherein L ^AB2 is a bond, a 5 or 6 membered heterocycloalkylene or heteroarylene, phenylene, -(C ₂ -C ₄ )alkynylene, -SO ₂ - or -NH-; and zz1 and zz2 are independently an integer from 0 to 10. [0037] In some embodiments, L ^AB is -(CH ₂ ) _zz1 (CH ₂ O) _zz2 -, wherein zz1 and zz2 are each independently an integer from 0 to 10. [0038] In some embodiments, L ^AB is a PEG linker. [0039] In some embodiments, B is a monovalent form of a compound selected from [0040] In an aspect is provided a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. [0041] In an aspect is provided a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof. [0042] In an aspect is provided a method of treating cancer in a subject comprising a Ras mutant protein, the method comprising: inhibiting the Ras mutant protein of said subject by administering to said subject a compound, wherein compound is characterized in that upon contacting the Ras mutant protein, said Ras mutant protein exhibits reduced Ras signaling output. [0043] In some embodiments, the cancer is a solid tumor. [0044] In some embodiments, the cancer is a hematological cancer. [0045] In some embodiments of a method described herein, the compound is a compound described herein. [0046] In an aspect is provided a method of modulating signaling output of a Ras protein, comprising contacting a Ras protein with an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the signaling output of the Ras protein. [0047] In an aspect is provided a method of inhibiting cell growth, comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, to a cell expressing a Ras protein, thereby inhibiting growth of said cells. [0048] In some embodiments of the methods described herein, the method comprises administering an additional agent. [0049] In some embodiments, the additional agent comprises (1) an inhibitor of MEK; (2) an inhibitor of epidermal growth factor receptor (EGFR) and/or of mutants thereof; (3) an immunotherapeutic agent; (4) a taxane; (5) an anti- metabolite; (6) an inhibitor of FGFR1 and/or FGFR2 and/or FGFR3 and/or of mutants thereof; (7) a mitotic kinase inhibitor; (8) an anti-angiogenic drug; (9) a topoisomerase inhibitor; (10) a platinum-containing compound; (12) an inhibitor of c-MET and/or of mutants thereof; (13) an inhibitor of BCR-ABL and/or of mutants thereof; (14) an inhibitor of ErbB2 (Her2) and/or of mutants thereof; (15) an inhibitor of AXL and/or of mutants thereof; (16) an inhibitor of NTRK1 and/or of mutants thereof; (17) an inhibitor of RET and/or of mutants thereof; (18) an inhibitor of A-Raf and/or B-Raf and/or C-Raf and/or of mutants thereof; (19) an inhibitor of ERK and/or of mutants thereof; (20) an MDM2 inhibitor; (21) an inhibitor of mTOR; (23) an inhibitor of IGF1/2 and/or of IGF1-R; (24) an inhibitor of CDK9; (25) an inhibitor of farnesyl transferase; (26) an inhibitor of SHIP pathway; (27) an inhibitor of SRC; (28) an inhibitor of JAK; (29) a PARP inhibitor, (31) a ROS1 inhibitor; (32) an inhibitor of SHP pathway, or (33) an inhibitor of Src, FLT3, HDAC, VEGFR, PDGFR, LCK, Bcr-Abl or AKT; (34) an inhibitor of KrasG12C mutant; (35) a SHC inhibitor (e.g., PP2, AID371185); (36) a GAB inhibitor; (38) a PI-3 kinase inhibitor; (39) a MARPK inhibitor; (40) CDK4/6 inhibitor; (41) MAPK inhibitor; (42) SHP2 inhibitor; (43) checkpoint immune blockade agents; (44) or SOS1 inhibitor; or (45) a SOS 2 inhibitor. [0050] In some embodiments, the additional agent comprises an inhibitor of SHP2 selected from RMC-4630, ERAS- , [0051] In embodiments, the additional agent comprises an inhibitor of SOS selected from RMC-5845, BI-1701963, [0052] In some embodiments, the additional agent comprises an inhibitor of EGFR selected from afatinib, erlotinib, gefitinib, lapatinib, cetuximab panitumumab, osimertinib, olmutinib, and EGF-816. [0053] In some embodiments, the additional agent comprises an inhibitor of MEK selected from trametinib, cobimetinib, binimetinib, selumetinib, refametinib, and AZD6244. [0054] In some embodiments, the additional agent comprises an inhibitor of ERK selected from ulixertinib, MK- 8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, and ravoxertinib. [0055] In some embodiments, the additional agent comprises an inhibitor of CDK4/6 selected from palbociclib, ribociclib, and abemaciclib. [0056] In some embodiments, the additional agent comprises an inhibitor of BRAF selected from Sorafenib, Vemurafenib, Dabrafenib, Encorafenib, regorafenib, and GDC-879. INCORPORATION BY REFERENCE [0057] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS [0058] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: [0059] FIG.1 depicts a sequence alignment of various wild type Ras proteins including K-Ras, H-Ras, N-Ras, RalA, RalB, from top to bottom. DETAILED DESCRIPTION [0060] The practice of some embodiments disclosed herein employ, unless otherwise indicated, conventional techniques of immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics and recombinant DNA, which are within the skill of the art. See for example Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4 ^th Edition (2012); the series Current Protocols in Molecular Biology (F. M. Ausubel, et al. eds.); the series Methods In Enzymology (Academic Press, Inc.), PCR 2: A Practical Approach (M.J. MacPherson, B.D. Hames and G.R. Taylor eds. (1995)), Harlow and Lane, eds. (1988) Antibodies, A Laboratory Manual, and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6 ^th Edition (R.I. Freshney, ed. (2010)). [0061] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood to which the claimed subject matter belongs. In the event that there are a plurality of definitions for terms herein, those in this section prevail. All patents, patent applications, publications and published nucleotide and amino acid sequences (e.g., sequences available in GenBank or other databases) referred to herein are incorporated by reference. Where reference is made to a URL or other such identifier or address, it is understood that such identifiers can change and particular information on the internet can come and go, but equivalent information can be found by searching the internet. Reference thereto evidences the availability and public dissemination of such information. [0062] It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed. In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting. [0063] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. [0064] Definition of standard chemistry terms may be found in reference works, including but not limited to, Carey and Sundberg “Advanced Organic Chemistry 4 ^th Ed.” Vols. A (2000) and B (2001), Plenum Press, New York. Unless otherwise indicated, conventional methods of mass spectroscopy, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques and pharmacology. [0065] Unless specific definitions are provided, the nomenclature employed in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those recognized in the field. Standard techniques can be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients. Standard techniques can be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Reactions and purification techniques can be performed e.g., using kits of manufacturer’s specifications or as commonly accomplished in the art or as described herein. The foregoing techniques and procedures can be generally performed of conventional methods and as described in various general and more specific references that are cited and discussed throughout the present specification. [0066] It is to be understood that the methods and compositions described herein are not limited to the particular methodology, protocols, cell lines, constructs, and reagents described herein and as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the methods, compounds, compositions described herein. [0067] As used herein, C ₁ -C _x includes C ₁ -C ₂ , C ₁ -C ₃ ... C ₁ -C _x . C ₁ -C _x refers to the number of carbon atoms that make up the moiety to which it designates (excluding optional substituents). [0068] An “alkyl” group refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation. In some embodiments, the “alkyl” group may have 1 to 18, 1 to 12, 1 to 10, 1 to 8, or 1 to 6 carbon atoms (whenever it appears herein, a numerical range such as “1 to 6” refers to each integer in the given range; e.g., “1 to 6 carbon atoms” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated). The alkyl group of the compounds described herein may be designated as “C ₁ -C ₆ alkyl” or similar designations. By way of example only, “C ₁ -C ₆ alkyl” indicates that there are one to six carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, iso-pentyl, neo- pentyl, and hexyl. Alkyl groups can be substituted or unsubstituted. Depending on the structure, an alkyl group can be a monoradical or a diradical (i.e., an alkylene group). [0069] An “alkoxy” refers to a “-O-alkyl” group, where alkyl is as defined herein. [0070] The term “alkenyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond. Non-limiting examples of an alkenyl group include -CH=CH ₂ , -C(CH ₃ )=CH ₂ , -CH=CHCH ₃ , -CH=C(CH ₃ ) ₂ and –C(CH ₃ )=CHCH ₃ . In some embodiments, an alkenyl groups may have 2 to 6 carbons. Alkenyl groups can be substituted or unsubstituted. Depending on the structure, an alkenyl group can be a monoradical or a diradical (i.e., an alkenylene group). [0071] The term “alkynyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond. Non-limiting examples of an alkynyl group include –C≡CH, -C≡CCH ₃ , –C≡CCH ₂ CH ₃ and –C≡CCH ₂ CH ₂ CH ₃ . In some embodiments, an alkynyl group can have 2 to 6 carbons. Alkynyl groups can be substituted or unsubstituted. Depending on the structure, an alkynyl group can be a monoradical or a diradical (i.e., an alkynylene group). [0072] “Amino” refers to a -NH ₂ group. [0073] The term “alkylamine” or “alkylamino” refers to the -N(alkyl) _x H _y group, where alkyl is as defined herein and x and y are selected from the group x=1, y=1 and x=2, y=0. When x=2, the alkyl groups, taken together with the nitrogen to which they are attached, can optionally form a cyclic ring system. “Dialkylamino” refers to a -N(alkyl) ₂ group, where alkyl is as defined herein. [0074] The term “aromatic” refers to a planar ring having a delocalized ^-electron system containing 4n+2 ^ electrons, where n is an integer. Aromatic rings can be formed from five, six, seven, eight, nine, or more than nine atoms. Aromatics can be optionally substituted. The term “aromatic” includes both aryl groups (e.g., phenyl, naphthalenyl) and heteroaryl groups (e.g., pyridinyl, quinolinyl). [0075] As used herein, the term “aryl” refers to a monocyclic aromatic ring wherein each of the atoms forming the ring is a carbon atom (e.g., phenyl) or a polycyclic ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is carbocyclic and aromatic, 2) a bond to the remainder of the compound is directly bonded to a carbocyclic aromatic ring of the aryl ring system, and 3) the carbocyclic aromatic ring of the aryl ring system of 2) is not directly bonded (e.g., fused) to a heteroaryl ring in the polycyclic ring system. Aryl rings can be formed by five, six, seven, eight, nine, or more than nine carbon atoms. Aryl groups can be optionally substituted. Examples of aryl groups include, but are not limited to phenyl, and naphthalenyl. Depending on the structure, an aryl group can be a monoradical or a diradical (i.e., an arylene group). As used herein, the aryl radical is a monocyclic, bicyclic, or tricyclic ring system. In embodiments, an aryl is a monocyclic ring. In embodiments, an aryl is a fused ring polycyclic system. In embodiments, an aryl is a bridged ring polycyclic system. In some embodiments the aryl is a “fused ring aryl” wherein the aryl ring is fused with a cycloalkyl or a heterocycloalkyl ring. In embodiments, an aryl is a “fused bicyclic” aryl wherein the two rings of the aryl group share one bond. [0076] “Carboxy” refers to -CO ₂ H. In some embodiments, carboxy moieties may be replaced with a “carboxylic acid bioisostere”, which refers to a functional group or moiety that exhibits similar physical and/or chemical properties as a carboxylic acid moiety. A carboxylic acid bioisostere has similar biological properties to that of a carboxylic acid group. A compound with a carboxylic acid moiety can have the carboxylic acid moiety exchanged with a carboxylic acid bioisostere and have similar physical and/or biological properties when compared to the carboxylic acid-containing compound. For example, in one embodiment, a carboxylic acid bioisostere would ionize at physiological pH to roughly the same extent as a carboxylic acid group. Examples of bioisosteres of a carboxylic acid include, but are not limited to, and the like. [0077] The term “cycloalkyl” refers to a monocyclic carbocyclic saturated or partially unsaturated non-aromatic ring or a polycyclic carbocyclic (i.e., does not include heteroatom(s)) ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is carbocyclic saturated or partially unsaturated and non-aromatic, 2) a bond to the remainder of the compound is directly bonded to a carbocyclic saturated or partially unsaturated non-aromatic ring of the ring system, and 3) the carbocyclic saturated or partially unsaturated non-aromatic ring of the ring system of 2) is not directly bonded (e.g., fused or spirocyclic) to a heterocycloalkyl ring in the polycyclic ring system. Cycloalkyls may be saturated or partially unsaturated. In some embodiments, a cycloalkyl ring is a spirocyclic cycloalkyl ring. In embodiments, a cycloalkyl is a monocyclic ring. In embodiments, a cycloalkyl is a fused ring polycyclic system. In embodiments, a cycloalkyl is a bridged ring polycyclic system. In embodiments, a cycloalkyl is a spirocyclic polycyclic ring system. In some embodiments, cycloalkyl groups include groups having from 3 to 10 ring atoms. Depending on the structure, a cycloalkyl group can be a monoradical or a diradical (i.e., a cycloalkylene group). In embodiments, a cycloalkyl is a “fused bicyclic” cycloalkyl wherein the two rings of the cycloalkyl group share one bond. [0078] The terms “heteroaryl” or, alternatively, “heteroaromatic” refers to an monocyclic aryl group that includes one or more ring heteroatoms selected from nitrogen, oxygen and sulfur; or a polycyclic ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is aromatic and includes one or more heteroatoms selected from nitrogen, oxygen and sulfur and 2) a bond to the remainder of the compound is directly bonded to an aromatic ring including one or more heteroatoms selected from nitrogen, oxygen and sulfur or an aromatic ring directly bonded (e.g., fused) to an aromatic ring including one or more heteroatoms selected from nitrogen, oxygen and sulfur, of the aryl ring system. As used herein, the heteroaryl radical may be a monocyclic, bicyclic, or tricyclic ring system, wherein at least one of the rings in the ring system is fully unsaturated (i.e., aromatic) and includes a heteroatom. In embodiments, a heteroaryl is a monocyclic ring. In embodiments, a heteroaryl is a fused ring polycyclic system. In embodiments, a heteroaryl is a bridged ring polycyclic system. In some embodiments is a “fused ring heteroaryl” wherein the heteroaryl ring is fused with a cycloalkyl, aryl, or heterocycloalkyl ring. An N-containing “heteroaromatic” or “heteroaryl” moiety refers to an aromatic group in which at least one of the skeletal atoms of the ring is a nitrogen atom. Depending on the structure, a heteroaryl group can be a monoradical or a diradical (i.e., a heteroarylene group). In embodiments, a heteroaryl is a “fused bicyclic” heteroaryl wherein the two rings of the heteroaryl group share one bond. [0079] A “heterocycloalkyl” group or “heteroalicyclic” group refers to a cycloalkyl group, wherein at least one skeletal ring atom of a saturated or partially unsaturated non-aromatic ring is a heteroatom selected from nitrogen, oxygen, phosphorus, and sulfur. A heterocycloalkyl refers to a monocyclic saturated or partially unsaturated non- aromatic ring including one or more heteroatoms or a polycyclic ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is saturated or partially unsaturated, non-aromatic, and includes one or more heteroatoms and 2) a bond to the remainder of the compound is directly bonded to a ring of the ring system that is a saturated or partially unsaturated and non-aromatic ring that includes one or more heteroatoms or a non-aromatic ring directly bonded (e.g., fused, spiro) to a saturated or partially unsaturated and non-aromatic ring that includes one or more heteroatoms of the ring system. Heterocycloalkyls may be saturated or partially unsaturated. The term heterocycloalkyl also includes all ring forms of the carbohydrates, including but not limited to the monosaccharides, the disaccharides and the oligosaccharides. In some embodiments, a heterocycloalkyl ring is a spirocyclic heterocycloalkyl ring. In embodiments, a heterocycloalkyl is a monocyclic ring. In embodiments, a heterocycloalkyl is a fused ring polycyclic system. In embodiments, a heterocycloalkyl is a bridged ring polycyclic system. In embodiments, a heterocycloalkyl is a spirocyclic polycyclic ring system. Unless otherwise noted, heterocycloalkyls have from 2 to 13 carbons in the ring or ring system. It is understood that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocycloalkyl (i.e. skeletal atoms of the heterocycloalkyl ring). Depending on the structure, a heterocycloalkyl group can be a monoradical or a diradical (i.e., a heterocycloalkylene group). In embodiments, a heterocycloalkyl is a “fused bicyclic” heterocycloalkyl wherein the two rings of the heterocycloalkyl group share one bond. [0080] The term “halo” or, alternatively, “halogen” means fluoro, chloro, bromo and iodo. [0081] The abbreviations “Fmoc”, “Ac”, “Bn”, “PMB”, “Tr”, “Ts”, “Boc”, and “Cbz” are used in accordance with their well understood common meanings in Chemistry and mean the monovalent chemical substituents fluorenylmethyloxycarbonyl, acetyl, benzyl, p-methoxybenzyl, trityl or triphenylmethyl, tosyl, tert- butyloxycarbonyl, and carbobenzyloxy, respectively. The term “monovalent” is used herein in accordance with its well understood meaning in Chemistry and refers to the ability of a substituent to form one covalent bond with another substituent or compound capable of forming a covalent bond. In a related manner, the term “divalent” refers to a substituent or compound capable of forming two covalent bonds, for example a linker capable of covalently connecting two monovalent substituents or compounds. [0082] The term “haloalkyl” refers to an alkyl group that is substituted with one or more halogens. The halogens may the same or they may be different. Non-limiting examples of haloalkyls include -CH ₂ Cl, -CF ₃ , -CHF ₂ , - CH ₂ CF ₃ , -CF ₂ CF ₃ , and the like. [0083] The terms “fluoroalkyl” and “fluoroalkoxy” include alkyl and alkoxy groups, respectively, that are substituted with one or more fluorine atoms. Non-limiting examples of fluoroalkyls include -CF ₃ , -CHF ₂ , -CH ₂ F, - CH ₂ CF ₃ , -CF ₂ CF ₃ , -CF ₂ CF ₂ CF ₃ , -CF(CH ₃ ) ₃ , and the like. Non-limiting examples of fluoroalkoxy groups, include - OCF ₃ , -OCHF ₂ , -OCH ₂ F, -OCH ₂ CF ₃ , -OCF ₂ CF ₃ , -OCF ₂ CF ₂ CF ₃ , -OCF(CH ₃ ) ₂ , and the like. [0084] The term “heteroalkyl” refers to an alkyl radical where one or more skeletal chain atoms is selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. The heteroatom(s) may be placed at any interior position of the heteroalkyl group. Examples include, but are not limited to, -CH ₂ -O-CH ₃ , -CH ₂ -CH ₂ -O-CH ₃ , -CH ₂ -NH-CH ₃ , -CH ₂ -CH ₂ -NH-CH ₃ , -CH ₂ -N(CH ₃ )-CH ₃ , -CH ₂ -CH ₂ -NH-CH ₃ , - CH ₂ -CH ₂ -N(CH ₃ )-CH ₃ , -CH ₂ -S-CH ₂ -CH ₃ , -CH ₂ -CH ₂ -S(O)-CH ₃ , -CH ₂ -CH ₂ -S(O) ₂ -CH ₃ , -CH ₂ -NH-OCH ₃ , –CH ₂ -O- Si(CH ₃ )3, -CH ₂ -CH=N-OCH ₃ , and -CH=CH-N(CH ₃ )-CH ₃ . In addition, up to two heteroatoms may be consecutive, such as, by way of example, -CH ₂ -NH-OCH ₃ and -CH ₂ -O-Si(CH ₃ ) ₃ . Excluding the number of heteroatoms, a “heteroalkyl” may have from 1 to 6 carbon atoms. [0085] The term “heteroalkylene linker” refers to a divalent alkyl radical where one or more skeletal chain atoms is selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. In some embodiments, the heteroatom(s) may be placed at any interior position of the heteroalkyl group. In some embodiments, the heteroatom(s) may be placed at one or both terminal positions of the heteroalkylene linker (i.e., position(s) directly bonded to portion(s) of the molecule other than the heteroalkylene linker). Examples include, but are not limited to, -CH ₂ -O-CH ₂ -, -CH ₂ -CH ₂ -O-CH ₂ -, -CH ₂ -NH-CH ₂ -, -CH ₂ -CH ₂ -NH-CH ₂ -, -CH ₂ - N(CH ₃ )-CH ₂ -, -CH ₂ -CH ₂ -N(CH ₃ )-CH ₂ -, -CH ₂ -S-CH ₂ -CH ₂ -, -CH ₂ -CH ₂ -S(O)-CH ₂ -, -CH ₂ -CH ₂ -S(O) ₂ -CH ₂ -, -CH ₂ - NH-O-CH ₂ -, –CH ₂ -O-Si(CH ₃ ) ₂ -, -CH ₂ -CH=N-O-CH ₂ -, and -CH=CH-N(CH ₃ )-CH ₂ -. Examples include, but are not limited to, -CH ₂ -O-, -CH ₂ -CH ₂ -O-, -CH ₂ -NH-, -CH ₂ -CH ₂ -NH-, -CH ₂ -N(CH ₃ )-, -CH ₂ -CH ₂ -N(CH ₃ )-, -CH ₂ -S-, -CH ₂ - CH ₂ -S-, -CH ₂ -CH ₂ -S(O)-, -CH ₂ -CH ₂ -S(O) ₂ -, -CH ₂ -S(O)-, -CH ₂ -S(O) ₂ -, -CH ₂ -CH ₂ -CH ₂ -S(O)-, -CH ₂ -CH ₂ -CH ₂ - S(O) ₂ -, -CH ₂ -CH ₂ -CH ₂ -O-, -CH ₂ -CH ₂ -CH ₂ -O-, -CH ₂ -CH ₂ -CH ₂ -S-, -CH ₂ -CH ₂ -CH ₂ -S-, -CH ₂ -CH ₂ -CH ₂ -NH-, -CH ₂ - CH ₂ -CH ₂ -NH-, -CH ₂ -CH ₂ -CH ₂ -N(CH ₃ )-, -CH ₂ -CH ₂ -CH ₂ -N(CH ₃ )-, -CH ₂ -NH-O-, -O-Si(CH ₃ ) ₂ -, -CH ₂ -CH=N-O-, and -CH=CH-N(CH ₃ )-. Examples include, but are not limited to, -O-CH ₂ -, -O-CH ₂ -CH ₂ -, -NH-CH ₂ -, -NH-CH ₂ - CH ₂ -, -N(CH ₃ )-CH ₂ -, -N(CH ₃ )-CH ₂ -CH ₂ -, -S-CH ₂ -, -S-CH ₂ -CH ₂ -, -S(O)-CH ₂ -CH ₂ -, -S(O) ₂ -CH ₂ -CH ₂ -, -S(O)-CH ₂ -, -S(O) ₂ -CH ₂ -, -S(O)-CH ₂ -CH ₂ -CH ₂ -, -S(O) ₂ -CH ₂ -CH ₂ -CH ₂ -, -O-CH ₂ -CH ₂ -CH ₂ -, -O-CH ₂ -CH ₂ -CH ₂ -, -S-CH ₂ -CH ₂ - CH ₂ -, -S-CH ₂ -CH ₂ -CH ₂ -, -NH-CH ₂ -CH ₂ -CH ₂ -, -NH-CH ₂ -CH ₂ -CH ₂ -, -N(CH ₃ )-CH ₂ -CH ₂ -CH ₂ -, -N(CH ₃ )-CH ₂ -CH ₂ - CH ₂ -, -O-NH-CH ₂ -, -Si(CH ₃ ) ₂ -O-, -O-N=CH-CH ₂ -, and -N(CH ₃ )-CH=CH-. In addition, up to two heteroatoms may be consecutive, such as, by way of example, -CH ₂ -NH-O- and -O-Si(CH ₃ ) ₂ -. Examples include, but are not limited to, -P(O)(CH ₃ )-CH ₂ -, -P(O)(CH ₃ )-CH ₂ -CH ₂ -, -P(O)(CH ₃ )-CH ₂ -CH ₂ -CH ₂ -,-CH ₂ -P(O)(CH ₃ )-, -CH ₂ -CH ₂ -P(O)(CH ₃ )- , and -CH ₂ -CH ₂ -CH ₂ -P(O)(CH ₃ )-. In addition, up to two heteroatoms may be consecutive, such as, by way of example, -CH ₂ -NH-O- and -O-Si(CH ₃ ) ₂ -. A “heteroalkylene linker” may have from 2 to 4 main chain atoms unless specified otherwise. [0086] The term “oxo” refers to the =O radical. [0087] The term “polycyclic cycloalkyl-heterocycloalkyl” refers to a ring system comprising a carbocyclic non- aromatic ring and a heteroatom containing non-aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the carbocyclic non-aromatic ring. The ring system may be fused, bridged, or spirocyclic. [0088] The term “polycyclic cycloalkyl-aryl” refers to a ring system comprising a carbocyclic non-aromatic ring and a carbocyclic-aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the carbocyclic non-aromatic ring. The ring system may be fused or bridged. [0089] The term “polycyclic cycloalkyl-heteroaryl” refers to a ring system comprising a carbocyclic non-aromatic ring and a heteroatom containing aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the carbocyclic non-aromatic ring. The ring system may be fused or bridged. [0090] The term “polycyclic heterocycloalkyl-cycloalkyl” refers to a ring system comprising a heteroatom containing non-aromatic ring and a carbocyclic non-aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the heteroatom containing non- aromatic ring. The ring system may be fused, bridged, or spirocyclic. [0091] The term “polycyclic heterocycloalkyl-aryl” refers to a ring system comprising a heteroatom containing non- aromatic ring and a carbocyclic aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the heteroatom containing non-aromatic ring. The ring system may be fused or bridged. [0092] The term “polycyclic heterocycloalkyl-heteroaryl” refers to a ring system comprising a heteroatom containing non-aromatic ring and a heteroatom containing aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the heteroatom containing non-aromatic ring. The ring system may be fused, bridged, or spirocyclic. [0093] The term “polycyclic aryl-cycloalkyl” refers to a ring system comprising a carbocyclic aromatic ring and a carbocyclic non-aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the carbocyclic aromatic ring. The ring system may be fused or bridged. [0094] The term “polycyclic aryl-heterocycloalkyl” refers to a ring system comprising a carbocyclic aromatic ring and a heteroatom containing non-aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the carbocyclic aromatic ring. The ring system may be fused or bridged. [0095] The term “polycyclic aryl-heteroaryl” refers to a ring system comprising a carbocyclic aromatic ring and a heteroatom containing aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the carbocyclic aromatic ring. [0096] The term “polycyclic heteroaryl-cycloalkyl” refers to a ring system comprising a heteroatom containing aromatic ring and a carbocyclic non-aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the heteroatom containing aromatic ring. The ring system may be fused or bridged. [0097] The term “polycyclic heteroaryl-heterocycloalkyl” refers to a ring system comprising a heteroatom containing aromatic ring and a heteroatom containing non-aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the heteroatom containing aromatic ring. The ring system may be fused or bridged. [0098] The term “polycyclic heteroaryl-aryl” refers to a ring system comprising a heteroatom containing aromatic ring and a carbocyclic aromatic ring, wherein (i) the two rings share one or more atoms, and (ii) the ring system is bonded to the remainder of a compound through the heteroatom containing aromatic ring. [0099] Unless stated otherwise, hydrogen atoms are implied in structures depicted herein as necessary to satisfy the valence requirement. [00100] A waved line drawn across or at the end of a bond or a dashed bond “ “ are used interchangeably herein to denote where a bond disconnection or attachment occurs. For example, in the structure if R ¹ is 2-fluoro-6-hydroxyphenyl as in then R ¹ may be depicted as or [00101] The term “bond” or “single bond” refers to a chemical bond between two atoms, or two moieties when the atoms joined by the bond are considered to be part of larger substructure. [00102] The term “moiety” refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized chemical entities embedded in or appended to a molecule. [00103] The suffix “-di-yl” will be understood to mean the substituent or linker is a divalent substituent or linker. [00104] As used herein, the substituent “R” appearing by itself and without a number designation refers to a substituent selected from among from alkyl, haloalkyl, heteroalkyl, alkenyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon), and heterocycloalkyl. [00105] “Optional” or “optionally” means that a subsequently described event or circumstance may or may not occur and that the description includes instances when the event or circumstance occurs and instances in which it does not. [00106] The term “optionally substituted” or “substituted” means, unless otherwise specified, that the referenced group may be substituted with one or more additional group(s) individually and independently selected from alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, -OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, -CN, alkyne, C ₁ -C ₆ alkylalkyne, halo, acyl, acyloxy, -CO ₂ H, -CO ₂ -alkyl, nitro, haloalkyl, fluoroalkyl, and amino, including mono- and di-substituted amino groups (e.g. –NH ₂ , -NHR, - N® ₂ ), and the protected derivatives thereof. By way of example, an optional substituents may be L ^s R ^s , wherein each L ^s is independently selected from a bond, -O-, -C(=O)-, -S-, -S(=O)-, -S(=O) ₂ -, -NH-, -NHC(O)-, -C(O)NH-, S(=O) ₂ NH-, -NHS(=O) ₂ , -OC(O)NH-, -NHC(O)O-, -(C ₁ -C ₆ alkyl)-, or -(C ₂ -C ₆ alkenyl)-; and each R ^s is independently selected from among H, (C ₁ -C ₆ alkyl), (C ₃ -C ₈ cycloalkyl), aryl, heteroaryl, heterocycloalkyl, and C ₁ - C ₆ heteroalkyl. The protecting groups that may form the protective derivatives of the above substituents are found in sources such as Greene and Wuts, above. [00107] “Pharmaceutically acceptable salt” includes both acid and base addition salts. A pharmaceutically acceptable salt of any one of the compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. [00108] “Pharmaceutically acceptable acid addition salt” refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts that are formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and. aromatic sulfonic acids, etc. and include, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Exemplary salts thus include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinate suberates, sebacates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, and the like. Also contemplated are salts of amino acids, such as arginates, gluconates, and galacturonates (see, for example, Berge S.M. et al., “Pharmaceutical Salts,” Journal of Pharmaceutical Science, 66:1-19 (1997)). Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base forms with a sufficient amount of the desired acid to produce the salt according to methods and techniques with which a skilled artisan is familiar. [00109] “Pharmaceutically acceptable base addition salt” refers to those salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. Pharmaceutically acceptable base addition salts are, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins and the like. See Berge et al., supra. [00110] The terms “polypeptide”, “peptide” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. As used herein the term “amino acid” refers to either natural and/or unnatural or synthetic amino acids, including glycine and both the D or L optical isomers, and amino acid analogs and peptidomimetics. [00111] The terms “polynucleotide”, “nucleotide”, “nucleotide sequence”, “nucleic acid” and “oligonucleotide” are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three dimensional structure, and may perform any function, known or unknown. The following are non-limiting examples of polynucleotides: coding or non- coding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short-hairpin RNA (shRNA), micro-RNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A polynucleotide may comprise one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, such as peptide nucleic acid (PNA), Morpholino and locked nucleic acid (LNA), glycol nucleic acid (GNA), threose nucleic acid (TNA), 2’-fluoro, 2’-OMe, and phosphorothiolated DNA. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component or other conjugation target. [00112] As used herein, “expression” refers to the process by which a polynucleotide is transcribed from a DNA template (such as into and mRNA or other RNA transcript) and/or the process by which a transcribed mRNA is subsequently translated into peptides, polypeptides, or proteins. Transcripts and encoded polypeptides may be collectively referred to as “gene product.” If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell. [00113] The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, simians, humans, farm animals, sport animals, and pets. Tissues, cells, and their progeny of a biological entity obtained in vivo or cultured in vitro are also encompassed. [00114] The terms “agent” or “therapeutic agent”, “therapeutic capable agent” or “treatment agent” are used interchangeably and refer to a molecule or compound that confers some beneficial effect upon administration to a subject. The beneficial effect includes enablement of diagnostic determinations; amelioration of a disease, symptom, disorder, or pathological condition; reducing or preventing the onset of a disease, symptom, disorder or condition; and generally counteracting a disease, symptom, disorder or pathological condition. [00115] As used herein, “treatment” or “treating,” or “palliating” or “ameliorating” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to a therapeutic benefit and/or a prophylactic benefit. By therapeutic benefit is meant any therapeutically relevant improvement in or effect on one or more diseases, conditions, or symptoms under treatment. For prophylactic benefit, the compositions may be administered to a subject at risk of developing a particular disease, condition, or symptom, or to a subject reporting one or more of the physiological symptoms of a disease, even though the disease, condition, or symptom may not have yet been manifested. Typically, prophylactic benefit includes reducing the incidence and/or worsening of one or more diseases, conditions, or symptoms under treatment (e.g. as between treated and untreated populations, or between treated and untreated states of a subject). [00116] The term “effective amount” or “therapeutically effective amount” refers to the amount of an agent that is sufficient to effect beneficial or desired results. The therapeutically effective amount may vary depending upon one or more of: the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the manner of administration and the like, which can readily be determined by one of ordinary skill in the art. An effective amount of an active agent may be administered in a single dose or in multiple doses. A component may be described herein as having at least an effective amount, or at least an amount effective, such as that associated with a particular goal or purpose, such as any described herein. The term “effective amount” also applies to a dose that will provide an image for detection by an appropriate imaging method. The specific dose may vary depending on one or more of: the particular agent chosen, the dosing regimen to be followed, whether it is administered in combination with other compounds, timing of administration, the tissue to be imaged, and the physical delivery system in which it is carried. [00117] The term “in vivo” refers to an event that takes place in a subject’s body. [00118] The term “ex vivo” refers to an event that first takes place outside of the subject’s body for a subsequent in vivo application into a subject’s body. For example, an ex vivo preparation may involve preparation of cells outside of a subject’s body for the purpose of introduction of the prepared cells into the same or a different subject’s body. [00119] The term “in vitro” refers to an event that takes place outside of a subject’s body. For example, an in vitro assay encompasses any assay run outside of a subject’s body. In vitro assays encompass cell-based assays in which cells alive or dead are employed. In vitro assays also encompass a cell-free assay in which no intact cells are employed. [00120] The term “Ras” or “RAS” refers to a protein in the Rat sarcoma (Ras) superfamily of small GTPases, such as in the Ras subfamily. The Ras superfamily includes, but is not limited to, the Ras subfamily, Rho subfamily, Rab subfamily, Rap subfamily, Arf subfamily, Ran subfamily, Rheb subfamily, RGK subfamily, Rit subfamily, Miro subfamily, and Unclassified subfamily. In some embodiments, a Ras protein is selected from the group consisting of KRAS (also used interchangeably herein as K-Ras, K-ras, Kras), HRAS (or H-Ras), NRAS (or N-Ras), MRAS (or M-Ras), ERAS (or E-Ras), RRAS2 (or R-Ras2), RALA (or RalA), RALB (or RalB), RIT1, and any combination thereof, such as from KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof. The terms “mutant Ras” and “Ras mutant,” as used interchangeably herein, refer to a Ras protein with one or more amino acid mutations, such as with respect to a common reference sequence such as a wild-type (WT) sequence. In some embodiments, a mutant Ras is selected from a mutant KRAS, mutant HRAS, mutant NRAS, mutant MRAS, mutant ERAS, mutant RRAS2, mutant RALA, mutant RALB, mutant RIT1, and any combination thereof, such as from a mutant KRAS, mutant HRAS, mutant NRAS, mutant RALA, mutant RALB, and any combination thereof. In some embodiments, a mutation can be an introduced mutation, a naturally occurring mutation, or a non-naturally occurring mutation. In some embodiments, a mutation can be a substitution (e.g., a substituted amino acid), insertion (e.g., addition of one or more amino acids), or deletion (e.g., removal of one or more amino acids). In some embodiments, two or more mutations can be consecutive, non-consecutive, or a combination thereof. In some embodiments, a mutation can be present at any position of Ras. In some embodiments, a mutation can be present at position 12, 13, 62, 92, 95, or any combination thereof of Ras of SEQ ID No.1 when optimally aligned. In some embodiments, a mutant Ras may comprise about or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more than 50 mutations. In some embodiments, a mutant Ras may comprise up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 mutations. In some embodiments, the mutant Ras is about or up to about 500, 400, 300, 250, 240, 233, 230, 220, 219, 210, 208, 206, 204, 200, 195, 190, 189, 188, 187, 186, 185, 180, 175, 174, 173, 172, 171, 170, 169, 168, 167, 166, 165, 160, 155, 150, 125, 100, 90, 80, 70, 60, 50, or fewer than 50 amino acids in length. In some embodiments, an amino acid of a mutation is a proteinogenic, natural, standard, non-standard, non-canonical, essential, non-essential, or non-natural amino acid. In some embodiments, an amino acid of a mutation has a positively charged side chain, a negatively charged side chain, a polar uncharged side chain, a non-polar side chain, a hydrophobic side chain, a hydrophilic side chain, an aliphatic side chain, an aromatic side chain, a cyclic side chain, an acyclic side chain, a basic side chain, or an acidic side chain. In some embodiments, a mutation comprises a reactive moiety. In some embodiments, a substituted amino acid comprises a reactive moiety. In some embodiments, a mutant Ras can be further modified, such as by conjugation with a detectable label. In some embodiments, a mutant Ras is a full-length or truncated polypeptide. For example, a mutant Ras can be a truncated polypeptide comprising residues 1-169 or residues 11-183 (e.g., residues 11-183 of a mutant RALA or mutant RALB). [00121] As used herein, the term “corresponding to” or “corresponds to” as applied to an amino acid residue in a polypeptide sequence refers to the correspondence of such amino acid relative to a reference sequence when optimally aligned (e.g., taking into consideration of gaps, insertions and mismatches; wherein alignment may be primary sequence alignment or three dimensional structural alignment of the folded proteins). For instance, the serine residue in a Ras G12S mutant refers to the serine corresponding to residue 12 of SEQ ID No.4, which can serve as a reference sequence. For instance, the aspartate residue in a Ras G12D mutant refers to the aspartate corresponding to residue 12 of SEQ ID No.2, which can serve as a reference sequence. When an amino acid of a mutant Ras protein corresponds to an amino acid position in the WT Ras protein, it will be understood that although the mutant Ras protein amino acid may be a different amino acid (e.g., G12D wherein the wildtype G at position 12 is replaced by an aspartate at position 12 of SEQ ID. No.1), the mutant amino acid is at the position corresponding to the wildtype amino acid (e.g., of SEQ ID No.1). In embodiments, a modified Ras mutant protein disclosed herein may comprise truncations at C-terminus, or truncations at the N-terminal end preceding the serine residue. The residue at position 12 of the full-length protein in such N-terminal truncated modified mutant is still considered corresponding to position 12 of SEQ ID No.1. In addition, serine residue at position 12 of SEQ ID No.4 finds a corresponding residue in SEQ ID Nos.6 and 8. [00122] “Prodrug” as used herein is meant to indicate a compound that may be converted under physiological conditions or by solvolysis to a biologically active compound described herein. The term “prodrug” refers to a precursor of a biologically active compound that is pharmaceutically acceptable. A prodrug may be inactive when administered to a subject, but is converted in vivo to an active compound, for example, by hydrolysis. The prodrug compound may offer advantages of solubility, tissue compatibility and/or delayed release in a mammalian organism (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp.7-9, 21-24 (Elsevier, Amsterdam). A discussion of prodrugs is provided in Higuchi, T., et al., “Pro-drugs as Novel Delivery Systems,” A.C.S. Symposium Series, Vol. 14, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated in full by reference herein. A “prodrug” can be any covalently bonded carriers, that release the active compound in vivo when such prodrug is administered to a mammalian subject. Prodrugs of an active compound, as described herein, may be prepared by modifying functional groups present in the active compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent active compound. [00123] The terms “leaving group” is used herein in accordance with their well understood meanings in Chemistry and refers to an atom or group of atoms which breaks away from the rest of the molecule, taking with it the electron pair which used to be the bond between the leaving group and the rest of the molecule. [00124] A “degradation enhancer” is a compound capable of binding a ubiquitin ligase protein (e.g., E3 ubiquitin ligase protein) or a compound capable of binding a protein that is capable of binding to a ubiquitin ligase protein to form a protein complex capable of conjugating a ubiquitin protein to a target protein. In embodiments, the degradation enhancer is capable of binding to an E3 ubiquitin ligase protein or a protein complex comprising an E3 ubiquitin ligase protein. In embodiments, the degradation enhancer is capable of binding to an E2 ubiquitin- conjugating enzyme. In embodiments, the degradation enhancer is capable of binding to a protein complex comprising an E2 ubiquitin-conjugating enzyme and an E3 ubiquitin ligase protein. Compounds [00125] In an aspect is provided a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: Formula (I); W ¹ is N, N(R ^1b ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1b ) each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ) each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _{3- 12} cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 3-5 membered heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _{2- 11} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00126] In an aspect is provided a compound of Formula (I-2), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-2); W ² , W ³ , W ⁵ , W ⁶ , W ⁷ , R ⁷ , L ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , W ⁸ , W ⁹ , W ¹⁰ , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , R ^4c , R ^4d , R ^4a , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ are as recited in Formula (I); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); L ⁴ is selected from a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, - N(R ^4d )CR ^4c R ^4c -, -C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, - CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, -CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, - CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, - S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, - P(O)R ^4d O-, -CR ^4c R ^4c CR ^4c R ^4c CR ^4c R ^4c -, -OCR ^4c R ^4c CR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c CR ^4c R ^4c -, -C(O)CR ^4c R ^4c CR ^4c R ^4c -, -SCR ^4c R ^4c CR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c CR ^4c R ^4c -, -S(O)CR ^4c R ^4c CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c CR ^4c R ^4c -, - CR ^4c R ^4c CR ^4c R ^4c O-, -CR ^4c R ^4c CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c CR ^4c R ^4c C(O)-, -CR ^4c R ^4c CR ^4c R ^4c S-, - CR ^4c R ^4c CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c CR ^4c R ^4c S(O)-, and -CR ^4c R ^4c CR ^4c R ^4c P(O)R ^4d -; each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -N(=R ¹⁵ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; each R ^1a , R ^1b , R ^1d , and R ^1h is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ¹¹ is selected from a C _3-12 cycloalkyl, 3-12 membered heterocycloalkyl, C _6-12 aryl, and 5-12 membered heteroaryl; wherein each of C _3-12 cycloalkyl, 3-12 membered heterocycloalkyl, C _6-12 aryl, and 5-12 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3- 12cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, - C _0-6 alkyl-(C _6-12 aryl), -C _0-6 alkyl-(C _1-11 heteroaryl), C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -C _0-6 alkyl- (C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C _6-12 aryl), -C _{0- 6} alkyl-(C _1-11 heteroaryl), and C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _{2- 11} heterocycloalkyl, C _6-12 aryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ ), - S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-12 aryl, and C _1-11 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, -C _0-6 alkyl- (C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C _6-12 aryl), -C _{0- 6} alkyl-(C _1-11 heteroaryl), and C _1-11 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C _6- 12aryl), -C _0-6 alkyl-(C _1-11 heteroaryl), and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20d ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C _6-12 aryl), -C _0-6 alkyl-(C _1-11 heteroaryl), C _1-11 heteroaryl, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , =NR ²¹ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 12} cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, - C _0-6 alkyl-(C _6-12 aryl), -C _0-6 alkyl-(C _1-11 heteroaryl) and C _1-11 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ^21b is independently selected from hydrogen, halogen, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl, or two R ^21b are taken together with the carbon atom to which they are attached to form C _3-10 cycloalkyl or C _2-9 heterocycloalkyl; each of which is optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH; indicates a single or double bond such that all valences are satisfied. [00127] In an aspect is provided a compound of Formula (I-3), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-3); wherein W ² , W ³ , W ⁵ , W ⁶ , W ⁷ , R ⁷ , L ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , W ⁸ , W ⁹ , W ¹⁰ , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , L ⁴ , R ^4c , R ^4d , R ^4a , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ^1b , R ² , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ⁶ , R ^6a , R ^6b , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^1j , R ⁸ , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , and R ^21b are as recited in Formula (I) or Formula (I-2); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); R ¹¹ is ; W ¹⁴ and W ¹⁵ are independently selected from N(R ^11c ), C(R ^11c )(R ^11c ), N(H), C(H)(R ^11c ), CH ₂ , C(O), S, O, S(O), and S(O) ₂ ; W ¹⁶ and W ¹⁷ are independently selected from C(R ^11c )(R ^11c ), C(H)(R ^11c ), CH ₂ , C(O), S, O, S(O), and S(O) ₂ ; W ¹⁸ is selected from N, CH, and C(R ^11c ); s14 is an integer from 1 to 5; s15 is an integer from 0 to 5; s16 is an integer from 1 to 3; s17 is an integer from 1 to 3; s24 is an integer from 0 to 5; s25 is an integer from 0 to 5; s26 is an integer from 0 to 5; and s27 is an integer from 0 to 5. [00128] In an aspect is provided a compound of Formula (I-4), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-4); wherein W ² , W ³ , W ⁵ , W ⁶ , W ⁷ , R ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , W ⁸ , W ⁹ , W ¹⁰ , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , L ⁴ , R ^4c , R ^4d , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ^1b , R ² , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ⁶ , R ^6a , R ^6b , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^1j , R ⁸ , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , and R ^21b are as recited in Formula (I) or Formula (I-2); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); R ¹¹ is W ¹⁴ and W ¹⁵ are independently selected from N(R ^11c ), C(R ^11c )(R ^11c ), N(H), C(H)(R ^11c ), CH ₂ , C(O), S, O, S(O), and S(O) ₂ ; W ¹⁶ and W ¹⁷ are independently selected from C(R ^11c )(R ^11c ), C(H)(R ^11c ), CH ₂ , C(O), S, O, S(O), and S(O) ₂ ; W ¹⁸ is selected from N, CH, and C(R ^11c ); s14 is an integer from 1 to 5; s15 is an integer from 0 to 5; s16 is an integer from 1 to 3; s17 is an integer from 1 to 3; s24 is an integer from 0 to 5; s25 is an integer from 0 to 5; s26 is an integer from 0 to 5; and s27 is an integer from 0 to 5; L ⁷ is a bond; and R ^4a is independently a 3-4 membered heterocycloalkyl comprising at least one nitrogen ring atom and substituted with one, two, three, or four R ^4b . [00129] In embodiments of Formula (I), (I-2), (I-3), (I-4), (I-5), or (I-6), or a pharmaceutically acceptable salt or solvate thereof, W ⁵ is a C(R ⁵ ) or C(O); W ⁶ is N, C(R ⁶ ), or N(R ^6b ); W ⁷ is C(R ⁷ ); W ⁸ is C(R ⁸ ); W ² is C(R ² ); W ¹ is N; W ³ is N; W ⁹ is C; W ¹⁰ is C; R ⁷ , L ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , R ^4c , R ^4d , R ^4a , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ^1b , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ^6a , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , R ^21b , R ¹¹ , W ¹⁴ , W ¹⁵ , W ¹⁶ , W ¹⁷ , W ¹⁸ , s14, s15, s16, s17, s24, s25, s26, s27 are as recited in Formula (I), (I-2), (I-3), (I-4), (I-5), or (I-6); L ⁴ is -C(O)-, -CR ^4c R ^4c C(O)-, or -N(R ^4d )C(O)-; R ⁶ is independently selected from hydrogen, halogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -OR ¹² , -SR ¹² , and -N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, and C _2-9 heterocycloalkyl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, and C _2-9 heterocycloalkyl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, and C _2-9 heterocycloalkyl are optionally substituted with one, two, or three R ^20d ; R ⁸ is independently selected from hydrogen, halogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, -OR ¹² , -SR ¹² , and -N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, and C _2-9 heterocycloalkyl are optionally substituted with one, two, or three R ^20f ; and R ² is C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -OR ¹² , -SR ¹² , or -N(R ¹² )(R ¹³ ), wherein said C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, and C _2-9 heterocycloalkyl are optionally substituted with one, two, or three R ^20d . [00130] In embodiments of Formula (I), (I-2), (I-3), (I-4), (I-5), or (I-6), or a pharmaceutically acceptable salt or solvate thereof, W ⁵ is a C(H); W ⁶ is N or C(R ⁶ ); W ⁷ is C(R ⁷ ); W ⁸ is C(R ⁸ ); W ² is C(R ² ); W ¹ is N; W ³ is N; W ⁹ is C; W ¹⁰ is C; R ⁷ , L ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , L ⁴ , R ^4c , R ^4d , R ^4a , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ^1b , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ^6a , R ^6b , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , R ^21b , R ¹¹ , W ¹⁴ , W ¹⁵ , W ¹⁶ , W ¹⁷ , W ¹⁸ , s14, s15, s16, s17, s24, s25, s26, s27 are as recited in Formula (I), (I-2), (I-3), (I-4), (I-5), or (I-6); L ⁴ is -C(O)-, -CR ^4c R ^4c C(O)-, or -N(R ^4d )C(O)-; R ⁶ is independently selected from hydrogen and halogen; R ⁸ is independently selected from hydrogen and halogen; and R ² is -O-CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . [00131] In embodiments of Formula (I), (I-2), (I-3), (I-4), (I-5), or (I-6), or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁵ is a C(H); W ⁶ is N or C(R ⁶ ); W ⁷ is C(R ⁷ ); W ⁸ is C(R ⁸ ); W ² is C(R ² ); W ¹ is N; W ³ is N; W ⁹ is C; W ¹⁰ is C; R ⁷ , L ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , R ^4c , R ^4d , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ^1b , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ^6a , R ^6b , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , R ^21b , R ¹¹ , W ¹⁴ , W ¹⁵ , W ¹⁶ , W ¹⁷ , W ¹⁸ , s14, s15, s16, s17, s24, s25, s26, s27 are as recited in Formula (I), (I-2), (I-3), (I-4), (I-5), or (I-6); L ⁴ is -C(O)-, -CR ^4c R ^4c C(O)-, or -N(R ^4d )C(O)-; R ^4a is selected from R ⁶ is independently selected from hydrogen and halogen; R ⁷ is selected from R ⁸ is independently selected from hydrogen and halogen; and R ² is selected from [00132] In embodiments of Formula (I), (I-2), (I-3), (I-4), or (I-6), or a pharmaceutically acceptable salt or solvate thereof, W ⁵ is a C(H); W ⁶ is N or C(R ⁶ ); W ⁷ is C(R ⁷ ); W ⁸ is C(R ⁸ ); W ² is C(R ² ); W ¹ is N; W ³ is N; W ⁹ is C; W ¹⁰ is C; R ⁷ , L ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , R ^4c , R ^4d , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ^1b , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ^6a , R ^6b , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , R ^21b , R ¹¹ , W ¹⁴ , W ¹⁵ , W ¹⁶ , W ¹⁷ , W ¹⁸ , s14, s15, s16, s17, s24, s25, s26, s27 are as recited in Formula (I), (I-2), (I-3), (I-4), or (I-6); L ⁴ is -C(O)-, -CR ^4c R ^4c C(O)-, or -N(R ^4d )C(O)-; R ^4a is selected from R ⁶ is independently selected from hydrogen and halogen; R ⁷ is selected from R ⁸ is independently selected from hydrogen and halogen; and R ² is selected from [00133] In embodiments of Formula (I), (I-2), (I-5), or (I-6), or a pharmaceutically acceptable salt or solvate thereof, W ² , W ³ , W ⁵ , W ⁶ , W ⁷ , R ⁷ , L ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , W ⁸ , W ⁹ , W ¹⁰ , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , L ⁴ , R ^4c , R ^4d , R ^4a , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ^1b , R ² , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ⁶ , R ^6a , R ^6b , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^1j , R ⁸ , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , R ^21b , R ¹¹ , W ¹⁴ , W ¹⁵ , W ¹⁶ , W ¹⁷ , W ¹⁸ , s14, s15, s16, s24, s25, s26, s27 are as recited in Formula (I), (I-2), (I-5), or (I-6); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); R ¹¹ is W ¹⁹ is selected from CH and C(R ^11c ); and s37 is an integer from 0 to 3. [00134] In embodiments of a compound of Formula (I), (I-2), (I-3), (I-4), or (I-6), or a pharmaceutically acceptable salt or solvate thereof, W ⁵ is a C(H); W ⁶ is N, N(R ^6b ), or C(R ⁶ ); W ⁷ is C(R ⁷ ); W ⁸ is C(R ⁸ ) or N; W ² is C(R ² ) or C(O); W ¹ is N or N(R ^1j ); W ³ is N; W ⁹ is C; W ¹⁰ is C; R ⁷ , Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , R ^1c , R ¹⁰ , L ¹¹ , R ^11a , R ^11b , R ⁴ , R ^4c , R ^4d , R ¹³ , R ¹⁴ , R ^14a , R ¹⁵ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ¹ , R ² , R ^2b , R ³ , R ^3a , R ^3b , W ^5a , W ^5b , R ⁵ , R ^5a , R ^5b , R ^6a , R ^7a , R ^7c , R ^7d , R ^1a , R ^1b , R ^1d , R ^1h , R ^1j , R ^8a , R ^8b , R ^11c , R ^4b , R ¹² , R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , R ²⁰ⁱ , R ^21b are as recited in Formula (I), (I-2), (I-3), (I-4), or (I-6); R ⁶ is hydrogen or halogen; R ^6b is selected from hydrogen, C _1-6 alkyl, C _3-10 cycloalkyl, or C _2-9 heterocycloalkyl, wherein C _1-6 alkyl, C _3-10 cycloalkyl, or C _2-9 heterocycloalkyl are optionally substituted with one, two, or three R ^20c ; R ⁸ is hydrogen or halogen; R ^1b is phenyl or pyridyl, wherein said phenyl or pyridyl are optionally substituted with one, two, or three R ^20a ; L ⁷ is a bond; R ¹¹ is a 5-7 membered monocyclic nitrogen containing heterocycloalkyl, 7-12 membered spirocyclic bicyclic nitrogen containing heterocycloalkyl, 7-12 membered fused bicyclic nitrogen containing heterocycloalkyl, or 8- 10 membered bridged nitrogen containing heterocycloalkyl, wherein the 5-7 membered monocyclic nitrogen containing heterocycloalkyl, 7-12 membered spirocyclic bicyclic nitrogen containing heterocycloalkyl, 7-12 membered fused bicyclic nitrogen containing heterocycloalkyl, or 8-10 membered bridged nitrogen containing heterocycloalkyl is each substituted with one R ⁴ , and optionally substituted with one, two, or three R ^11c ; L ⁴ is -C(O)-, -CR ^4c R ^4c C(O)-, or -N(R ^4d )C(O)-; R ^4a is selected from , , , , , , R ² is -O-CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . [00135] In an aspect is provided a compound of Formula (I-5), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-5); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ); each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a W ^5b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from , Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl ring, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl ring system, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, - CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1- 11heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1- 6alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently selected from each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C ₂ - 1 ₁ heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _{1- 6} alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ²⁰ g, R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00136] In an aspect is provided a compound of Formula (I-6), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-6); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ); each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a W ^5b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl ring, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl ring system, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, - CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _{1- 11} heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1- 6alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 3-5 membered heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _{2- 11} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _{1- 6} alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl; wherein the compound is capable of covalently modifying a Ras protein; and indicates a single or double bond such that all valences are satisfied. [00137] In embodiments of a compound of Formulae (I), (I-1), (I-2), (I-3), or (I-4), or a pharmaceutically acceptable salt or solvate thereof, each R ^4a is independently selected from and L ¹¹ is a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, - N(R ^11b )CR ^11a R ^11a -, -C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, - CR ^11a R ^11a CR ^11a R ^11a , -CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, - CR ^11a R ^11a S(O)-, -CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, - C(O)N(R ^11b )-, -S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, - C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-. [00138] In embodiments of a compound of Formulae (I), (I-1), (I-2), (I-3), or (I-4), or a pharmaceutically acceptable salt or solvate thereof, L ¹¹ is a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , - OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, -C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, - P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , -CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, - CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, -CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, - N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, -S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, - OP(O)R ^11b -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; and the compound is capable of covalently modifying a Ras protein. [00139] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ¹ , R ^1a , R ^1b , R ^1c , R ^1d , R ^1h , R ¹ⁱ , or R ^1j ,) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II- 1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00140] In embodiments of the formulae above, R ¹ is independently hydrogen. In embodiments of the formulae above, R ¹ is independently-CN. In embodiments of the formulae above, R ¹ is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _{2- 6} alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _6-10 aryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently -OR ¹² . In embodiments of the formulae above, R ¹ is independently -C(O)OR ¹² . In embodiments of the formulae above, R ¹ is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ¹ is independently -C(O)R ¹⁵ . In embodiments of the formulae above, R ¹ is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00141] In embodiments of the formulae above, R ^1j is independently hydrogen. In embodiments of the formulae above, R ^1j is independently-CN. In embodiments of the formulae above, R ^1j is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1j is independently C ₂ - ₆ alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1j is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1j is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1j is independently C _6-10 aryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1j is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1j is independently -OR ¹² . In embodiments of the formulae above, R ^1j is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^1j is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1j is independently -C(O)R ¹⁵ . [00142] In embodiments of the formulae above, R ^1a is independently hydrogen. In embodiments of the formulae above, R ^1a is independently-CN. In embodiments of the formulae above, R ^1a is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1a is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1a is independently C _{2- 6} alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1a is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1a is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1a is independently C _6-10 aryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1a is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1a is independently -OR ¹² . In embodiments of the formulae above, R ^1a is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^1a is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1a is independently -C(O)R ¹⁵ . In embodiments of the formulae above, R ^1a is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00143] In embodiments of the formulae above, R ^1b is independently hydrogen. In embodiments of the formulae above, R ^1b is independently-CN. In embodiments of the formulae above, R ^1b is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1b is independently C ₂ - ₆ alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1b is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1b is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1b is independently C _6-10 aryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1b is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1b is independently -OR ¹² . In embodiments of the formulae above, R ^1b is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^1b is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1b is independently -C(O)R ¹⁵ . In embodiments of the formulae above, R ^1b is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00144] In embodiments of the formulae above, R ^1c is independently hydrogen. In embodiments of the formulae above, R ^1c is independently-CN. In embodiments of the formulae above, R ^1c is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1c is independently C ₂ - ₆ alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1c is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1c is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1c is independently C _6-10 aryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1c is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1c is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00145] In embodiments of the formulae above, R ^1c is hydrogen. In embodiments of the formulae above, R ^1c is halogen. In embodiments of the formulae above, R ^1c is -CN. In embodiments of the formulae above, R ^1c is C _1-6 alkyl. In embodiments of the formulae above, R ^1c is C _2-6 alkenyl. In embodiments of the formulae above, R ^1c is C ₂ - ₆ alkynyl. In embodiments of the formulae above, R ^1c is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^1c is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^1c is C _6-10 aryl. In embodiments of the formulae above, R ^1c is C _1-9 heteroaryl. [00146] In embodiments of the formulae above, R ^1c is C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _2-6 alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . [00147] In embodiments of the formulae above, R ^1c is -OR ¹² . In embodiments of the formulae above, R ^1c is -SR ¹² . In embodiments of the formulae above, R ^1c is -C(O)OR ¹² . In embodiments of the formulae above, R ^1c is - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -C(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^1c is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^1c is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). [00148] In embodiments of the formulae above, R ^1d is independently hydrogen. In embodiments of the formulae above, R ^1d is independently -CN. In embodiments of the formulae above, R ^1d is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1d is independently C ₂ - ₆ alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1d is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1d is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1d is independently C _6-10 aryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1d is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1d is independently -OR ¹² . In embodiments of the formulae above, R ^1d is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^1d is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1d is independently -C(O)R ¹⁵ . In embodiments of the formulae above, R ^1d is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00149] In embodiments of the formulae above, R ^1d is independently selected from hydrogen, halogen, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a . [00150] In embodiments of the formulae above, R ^1d is independently selected from hydrogen, -CN, C _1-6 alkyl, and C _1-6 haloalkyl, wherein C _1-6 alkyl is optionally substituted with one, two, or three R ²⁰ⁱ . [00151] In embodiments, R ^1h is selected from hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -C(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ C(O)N(R ¹² )(R ¹³ ), and -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, and C _2-6 alkynyl are optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1h is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00152] In embodiments of the formulae above, R ^1h is selected from hydrogen and -N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1h is hydrogen. In embodiments of the formulae above, R ^1h is -N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1h is -NH ₂ . [00153] In embodiments of the formulae above, R ^1h is hydrogen. In embodiments of the formulae above, R ^1h is- CN. In embodiments of the formulae above, R ^1h is C _1-6 alkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ¹ is C _2-6 alkenyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1h is C _2-6 alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1h is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1h is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1h is C _6-10 aryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1h is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^1h is -OR ¹² . In embodiments of the formulae above, R ^1h is -C(O)OR ¹² . In embodiments of the formulae above, R ^1h is -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1h is - C(O)R ¹⁵ . [00154] In embodiments of the formulae above, R ¹ⁱ is hydrogen. In embodiments of the formulae above, R ¹ⁱ is halogen. In embodiments of the formulae above, R ¹ⁱ is -CN. In embodiments of the formulae above, R ¹ⁱ is C _1-6 alkyl. In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkenyl. In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkynyl. In embodiments of the formulae above, R ¹ⁱ is C _3-10 cycloalkyl. In embodiments of the formulae above, R ¹ⁱ is C _{2- 9} heterocycloalkyl. In embodiments of the formulae above, R ¹ⁱ is C _6-10 aryl. In embodiments of the formulae above, R ¹ⁱ is C _1-9 heteroaryl. [00155] In embodiments of the formulae above, R ¹ⁱ is C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . [00156] In embodiments of the formulae above, R ¹ⁱ is -OR ¹² . In embodiments of the formulae above, R ¹ⁱ is -SR ¹² . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is - C(O)OR ¹² . In embodiments of the formulae above, R ¹ⁱ is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is - C(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -S(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is - OC(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is - CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). [00157] In embodiments of the formulae above, R ^1a is independently hydrogen. In embodiments of the formulae above, R ^1a is independently-CN. In embodiments of the formulae above, R ^1a is independently C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1a is independently C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1a is independently C _{2- 6} alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1a is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1a is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1a is independently C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1a is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1a is independently -OR ¹² . In embodiments of the formulae above, R ^1a is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^1a is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1a is independently -C(O)R ¹⁵ . [00158] In embodiments of the formulae above, R ^1b is independently hydrogen. In embodiments of the formulae above, R ^1b is independently-CN. In embodiments of the formulae above, R ^1b is independently C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1b is independently C _{2- 6} alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1b is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1b is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1b is independently C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1b is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1b is independently -OR ¹² . In embodiments of the formulae above, R ^1b is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^1b is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1b is independently -C(O)R ¹⁵ . [00159] In embodiments of the formulae above, R ^1c is independently hydrogen. In embodiments of the formulae above, R ^1c is independently-CN. In embodiments of the formulae above, R ^1c is independently C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is independently C ₂ - ₆ alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is independently C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . [00160] In embodiments of the formulae above, R ^1c is hydrogen. In embodiments of the formulae above, R ^1c is halogen. In embodiments of the formulae above, R ^1c is -CN. In embodiments of the formulae above, R ^1c is C _1-6 alkyl. In embodiments of the formulae above, R ^1c is C _2-6 alkenyl. In embodiments of the formulae above, R ^1c is C _{2- 6} alkynyl. In embodiments of the formulae above, R ^1c is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^1c is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^1c is C _6-10 aryl. In embodiments of the formulae above, R ^1c is C _1-9 heteroaryl. [00161] In embodiments of the formulae above, R ^1c is C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _2-6 alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1c is C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . [00162] In embodiments of the formulae above, R ^1c is -OR ¹² . In embodiments of the formulae above, R ^1c is -SR ¹² . In embodiments of the formulae above, R ^1c is -C(O)OR ¹² . In embodiments of the formulae above, R ^1c is - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -C(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^1c is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^1c is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^1c is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^1c is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). [00163] In embodiments of the formulae above, R ^1d is independently hydrogen. In embodiments of the formulae above, R ^1d is independently -CN. In embodiments of the formulae above, R ^1d is independently C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ is independently C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1d is independently C _{2- 6} alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1d is independently C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1d is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1d is independently C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1d is independently C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1d is independently -OR ¹² . In embodiments of the formulae above, R ^1d is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^1d is independently - OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1d is independently -C(O)R ¹⁵ . [00164] In embodiments of the formulae above, R ^1d is independently selected from hydrogen, halogen, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . [00165] In embodiments of the formulae above, R ^1d is independently selected from hydrogen, -CN, C _1-6 alkyl, and C _1-6 haloalkyl, wherein C _1-6 alkyl is optionally substituted with one, two, or three R ²⁰ⁱ . [00166] In embodiments, R ^1h is selected from hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -C(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ C(O)N(R ¹² )(R ¹³ ), and -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, and C _2-6 alkynyl are optionally substituted with one, two, or three R ²⁰ⁱ . [00167] In embodiments of the formulae above, R ^1h is selected from hydrogen and -N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1h is hydrogen. In embodiments of the formulae above, R ^1h is -N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1h is -NH ₂ . [00168] In embodiments of the formulae above, R ^1h is hydrogen. In embodiments of the formulae above, R ^1h is- CN. In embodiments of the formulae above, R ^1h is C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ is C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1h is C _2-6 alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1h is C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1h is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1h is C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1h is C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ^1h is -OR ¹² . In embodiments of the formulae above, R ^1h is -C(O)OR ¹² . In embodiments of the formulae above, R ^1h is -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^1h is - C(O)R ¹⁵ . [00169] In embodiments of the formulae above, R ¹ⁱ is hydrogen. In embodiments of the formulae above, R ¹ⁱ is halogen. In embodiments of the formulae above, R ¹ⁱ is -CN. In embodiments of the formulae above, R ¹ⁱ is C _1-6 alkyl. In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkenyl. In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkynyl. In embodiments of the formulae above, R ¹ⁱ is C _3-10 cycloalkyl. In embodiments of the formulae above, R ¹ⁱ is C _{2- 9} heterocycloalkyl. In embodiments of the formulae above, R ¹ⁱ is C _6-10 aryl. In embodiments of the formulae above, R ¹ⁱ is C _1-9 heteroaryl. [00170] In embodiments of the formulae above, R ¹ⁱ is C _1-6 alkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkenyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _2-6 alkynyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _3-10 cycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _6-10 aryl optionally substituted with one, two, or three R ²⁰ⁱ . In embodiments of the formulae above, R ¹ⁱ is C _1-9 heteroaryl optionally substituted with one, two, or three R ²⁰ⁱ . [00171] In embodiments of the formulae above, R ¹ⁱ is -OR ¹² . In embodiments of the formulae above, R ¹ⁱ is -SR ¹² . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is - C(O)OR ¹² . In embodiments of the formulae above, R ¹ⁱ is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is - C(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -S(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is - OC(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is - CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ¹ⁱ is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ¹ⁱ is -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). [00172] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ² or R ^2b ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00173] In embodiments of the formulae above, R ² is selected from , , ,

[00174] In embodiments of the formulae above, R ² is selected from , ,

, , , [00175] In embodiments of the formulae above, R ² is selected from

In embodiments of the formulae above, R ² is In embodimen ² ts of the formulae above, R is In embodiments of the formulae above, R ² is In embodiments of the formulae above, R ² is In embodiments of the formulae above, R ² is In embodiments of the formulae above, R ² is In embodiments of the formulae above, R ² is In embodiments of the formulae above, R ² is In embodiments of the formulae above, R ² is In embodiments of t ^{he formulae above, R2 is} . [00176] In embodiments of the formulae above, R ² is -O-CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d wherein R ^20d is independently halogen (e.g., F). In embodiments of the formulae above, R ² is -O- CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d wherein R ^20d is independently C _1-6 alkyl (e.g., methyl). In embodiments of the formulae above, R ² is In embodiments of the formulae above, R ² is I ² n embodiments of the formulae above, R is In embodiments of the formulae above, R ² is . In embodiments of the formulae above, R ² is [00177] In embodiments of the formulae above, R ² is hydrogen. In embodiments of the formulae above, R ² is halogen. In embodiments of the formulae above, R ² is -CN. In embodiments of the formulae above, R ² is C _1-6 alkyl. In embodiments of the formulae above, R ² is C _2-6 alkenyl. In embodiments of the formulae above, R ² is C _2-6 alkynyl. In embodiments of the formulae above, R ² is C _3-10 cycloalkyl. In embodiments of the formulae above, R ² is C _{2- 9} heterocycloalkyl. In embodiments of the formulae above, R ² is C _6-10 aryl. In embodiments of the formulae above, R ² is C _1-9 heteroaryl. [00178] In embodiments of the formulae above, R ² is C _1-6 alkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ² is C _2-6 alkenyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ² is C _2-6 alkynyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ² is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ² is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ² is C _6-10 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ² is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20d . [00179] In embodiments of the formulae above, R ² is -OR ¹² . In embodiments of the formulae above, R ² is -SR ¹² . In embodiments of the formulae above, R ² is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is -C(O)OR ¹² . In embodiments of the formulae above, R ² is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ² is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ² is -C(O)R ¹⁵ . In embodiments of the formulae above, R ² is -S(O)R ¹⁵ . In embodiments of the formulae above, R ² is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ² is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ² is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ² is -S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ² is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ² is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ² is -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ² is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ¹ is independently -N(=R ¹⁵ ). [00180] In embodiments of the formulae above, R ^2b is hydrogen. In embodiments of the formulae above, R ^2b is halogen. In embodiments of the formulae above, R ^2b is -CN. In embodiments of the formulae above, R ^2b is C _{1- 6} alkyl. In embodiments of the formulae above, R ^2b is C _2-6 alkenyl. In embodiments of the formulae above, R ^2b is C ₂ - ₆ alkynyl. In embodiments of the formulae above, R ^2b is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^2b is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^2b is C _6-10 aryl. In embodiments of the formulae above, R ^2b is C _1-9 heteroaryl. [00181] In embodiments of the formulae above, R ^2b is C _1-6 alkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^2b is C _2-6 alkenyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^2b is C _2-6 alkynyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^2b is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^2b is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^2b is C _6-10 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^2b is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20d . [00182] In embodiments of the formulae above, R ^2b is -OR ¹² . In embodiments of the formulae above, R ^2b is -SR ¹² . In embodiments of the formulae above, R ^2b is -C(O)OR ¹² . In embodiments of the formulae above, R ^2b is - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^2b is -C(O)R ¹⁵ . In embodiments of the formulae above, R ^2b is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^2b is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^2b is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^2b is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^2b is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^2b is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^2b is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^2b is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^2b is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^2b is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^2b is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^2b is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00183] In embodiments of the formulae above, R ^2b is selected from

[00184] In embodiments of the formulae above, R ^2b is selected from

[00185] In embodiments of the formulae above, R ^2b is -O-CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d wherein R ^20d is independently halogen (e.g., F). In embodiments of the formulae above, R ^2b is -O-CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d wherein R ²⁰ is independently C _{1- 6} alkyl (e.g., methyl). In embodiments of the formulae above, R ^2b is In embodiments of the formulae above, R ^2b is In embodiments of the formulae above, R ^2b is In embodiments of the formulae above, R ^2b is In em ^2b bodiments of the formulae above, R is [00186] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ³ , R ^3a , or R ^3b ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00187] In embodiments of the formulae above, R ³ is hydrogen. In embodiments of the formulae above, R ³ is-CN. In embodiments of the formulae above, R ³ is C _1-6 alkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ³ is C _2-6 alkenyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ³ is C _2-6 alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ³ is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ³ is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ³ is C _6-10 aryl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ³ is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ³ is -OR ¹² . In embodiments of the formulae above, R ³ is -C(O)OR ¹² . In embodiments of the formulae above, R ³ is -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ³ is - C(O)R ¹⁵ . In embodiments of the formulae above, R ³ is halogen. In embodiments of the formulae above, R ³ is - N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ³ is -NH ₂ . In embodiments of the formulae above, R ³ is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00188] In embodiments of the formulae above, R ^3a is hydrogen. In embodiments of the formulae above, R ^3a is- CN. In embodiments of the formulae above, R ^3a is C _1-6 alkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3a is C _2-6 alkenyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3a is C _2-6 alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^3a is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3a is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3a is C _6-10 aryl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3a is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3a is -OR ¹² . In embodiments of the formulae above, R ^3a is -C(O)OR ¹² . In embodiments of the formulae above, R ^3a is -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^3a is - C(O)R ¹⁵ . In embodiments of the formulae above, R ^3a is halogen. In embodiments of the formulae above, R ^3a is - N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^3a is -NH ₂ . In embodiments of the formulae above, R ^3a is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00189] In embodiments of the formulae above, R ^3b is hydrogen. In embodiments of the formulae above, R ^3b is- CN. In embodiments of the formulae above, R ^3b is C _1-6 alkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3b is C _2-6 alkenyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3b is C _2-6 alkynyl optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^3b is C _2-6 alkynyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3b is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3b is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3b is C _6-10 aryl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3b is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20b . In embodiments of the formulae above, R ^3b is -OR ¹² . In embodiments of the formulae above, R ^3b is -C(O)OR ¹² . In embodiments of the formulae above, R ^3b is -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^3b is - C(O)R ¹⁵ . In embodiments of the formulae above, R ^3b is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00190] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of L ⁴ ) are applicable to compounds of Formulae (I), (I-2), (I-3), (I-4), (I-5), (I-6), (I-1), (II), and (II-1), or a pharmaceutically acceptable salt or solvate thereof. [00191] In some embodiments of Formulae (I), (I-2), (I-3), (I-4), (I-5), (I-6), (I-1), (II), and (II-1), L ⁴ is selected from a bond, -C(O)-, -NHC(O)-, and-C(O)NH-. [00192] In embodiments of the formulae above, L ⁴ is a bond. In embodiments of the formulae above, L ⁴ is -O-. In embodiments of the formulae above, L ⁴ is -N(R ^4d )- . In embodiments of the formulae above, L ⁴ is -C(O)- . In embodiments of the formulae above, L ⁴ is -S-. In embodiments of the formulae above, L ⁴ is -S(O) ₂ -. In embodiments of the formulae above, L ⁴ is -S(O)- . In embodiments of the formulae above, L ⁴ is -P(O)R ^4d -. In embodiments of the formulae above, L ⁴ is CR ^4c R ^4c . In embodiments of the formulae above, L ⁴ is -OCR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -N(R ^4d )CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is - C(O)CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -SCR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -S(O) ₂ CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -S(O)CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -P(O)R ^4d CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c . In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c O-. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c N(R ^4d )- . In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c C(O)- . In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c S- . In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c S(O) ₂ -. In embodiments of the formulae above, L ⁴ is - CR ^4c R ^4c S(O)- . In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c P(O)R ^4d -. In embodiments of the formulae above, L ⁴ is -N(R ^4d )C(O)- . In embodiments of the formulae above, L ⁴ is -N(R ^4d )S(O) ₂ -. In embodiments of the formulae above, L ⁴ is -N(R ^4d )S(O)- . In embodiments of the formulae above, L ⁴ is -N(R ^4d )P(O)R ^4d -. In embodiments of the formulae above, L ⁴ is -C(O)N(R ^4d )- . In embodiments of the formulae above, L ⁴ is - S(O) ₂ N(R ^4d )- . In embodiments of the formulae above, L ⁴ is -S(O)N(R ^4d )- . In embodiments of the formulae above, L ⁴ is -P(O)R ^4d N(R ^4d )- . In embodiments of the formulae above, L ⁴ is -OC(O)- . In embodiments of the formulae above, L ⁴ is -OS(O) ₂ -. In embodiments of the formulae above, L ⁴ is -OS(O)- . In embodiments of the formulae above, L ⁴ is -OP(O)R ^4d -. In embodiments of the formulae above, L ⁴ is -C(O)O-. In embodiments of the formulae above, L ⁴ is -S(O) ₂ O-. In embodiments of the formulae above, L ⁴ is -S(O)O-. In embodiments of the formulae above, L ⁴ is -P(O)R ^4d O-. [00193] In embodiments of the formulae above, L ⁴ is a bond. In embodiments of the formulae above, L ⁴ is -O-. In embodiments of the formulae above, L ⁴ is -NH- . In embodiments of the formulae above, L ⁴ is -C(O)- . In embodiments of the formulae above, L ⁴ is -S-. In embodiments of the formulae above, L ⁴ is -S(O) ₂ -. In embodiments of the formulae above, L ⁴ is -S(O)- . In embodiments of the formulae above, L ⁴ is -P(O)CH ₃ -. In embodiments of the formulae above, L ⁴ is CH ₂ . In embodiments of the formulae above, L ⁴ is -OCH ₂ -. In embodiments of the formulae above, L ⁴ is -N(H)CH ₂ -. In embodiments of the formulae above, L ⁴ is -C(O)CH ₂ -. In embodiments of the formulae above, L ⁴ is -SCH ₂ -. In embodiments of the formulae above, L ⁴ is -S(O) ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is -S(O)CH ₂ -. In embodiments of the formulae above, L ⁴ is - P(O)(CH ₃ )CH ₂ -. In embodiments of the formulae above, L ⁴ is -CH ₂ CH ₂ . In embodiments of the formulae above, L ⁴ is -CH ₂ O-. In embodiments of the formulae above, L ⁴ is -CH ₂ N(H)- . In embodiments of the formulae above, L ⁴ is -CH ₂ C(O)- . In embodiments of the formulae above, L ⁴ is -CH ₂ S-. In embodiments of the formulae above, L ⁴ is - CH ₂ S(O) ₂ -. In embodiments of the formulae above, L ⁴ is -CH ₂ S(O)- . In embodiments of the formulae above, L ⁴ is -CH ₂ P(O)CH ₃ -. In embodiments of the formulae above, L ⁴ is -N(H)C(O)- . In embodiments of the formulae above, L ⁴ is -N(H)S(O) ₂ -. In embodiments of the formulae above, L ⁴ is -N(H)S(O)- . In embodiments of the formulae above, L ⁴ is -N(H)P(O)CH ₃ -. In embodiments of the formulae above, L ⁴ is -C(O)N(H)- . In embodiments of the formulae above, L ⁴ is -S(O) ₂ N(H)- . In embodiments of the formulae above, L ⁴ is -S(O)N(H)- . In embodiments of the formulae above, L ⁴ is -P(O)(CH ₃ )N(H)- . In embodiments of the formulae above, L ⁴ is -OC(O)- . In embodiments of the formulae above, L ⁴ is -OS(O) ₂ -. In embodiments of the formulae above, L ⁴ is -OS(O)- . In embodiments of the formulae above, L ⁴ is -OP(O)CH ₃ -. In embodiments of the formulae above, L ⁴ is -C(O)O-. In embodiments of the formulae above, L ⁴ is -S(O) ₂ O-. In embodiments of the formulae above, L ⁴ is -S(O)O-. In embodiments of the formulae above, L ⁴ is -P(O)(CH ₃ )O-. [00194] In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -OCR ^4c R ^4c CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -N(R ^4d )CR ^4c R ^4c CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -C(O)CR ^4c R ^4c CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is - SCR ^4c R ^4c CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -S(O) ₂ CR ^4c R ^4c CR ^4c R ^4c -. In embo embodiments of the formulae above diments, L ⁴ is -S(O)CR ^4c R ^4c CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is - P(O)R ^4d CR ^4c R ^4c CR ^4c R ^4c -. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c O-. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c N(R ^4d )- . In embodiments of the formulae above, L ⁴ is - CR ^4c R ^4c CR ^4c R ^4c C(O) -. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c S-. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c S(O) ₂ -. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c S(O)-. In embodiments of the formulae above, L ⁴ is -CR ^4c R ^4c CR ^4c R ^4c P(O)R ^4d -. [00195] In embodiments of the formulae above, L ⁴ is -CH ₂ CH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is - OCH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is -N(H)CH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is -C(O)CH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is -SCH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is -S(O) ₂ CH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is -S(O)CH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is -P(O)(CH ₃ )CH ₂ CH ₂ -. In embodiments of the formulae above, L ⁴ is - CH ₂ CH ₂ O-. In embodiments of the formulae above, L ⁴ is -CH ₂ CH ₂ N(H)- . In embodiments of the formulae above, L ⁴ is - CH ₂ CH ₂ C(O) -. In embodiments of the formulae above, L ⁴ is -CH ₂ CH ₂ S-. In embodiments of the formulae above, L ⁴ is -CH ₂ CH ₂ S(O) ₂ -. In embodiments of the formulae above, L ⁴ is -CH ₂ CH ₂ S(O)-. In embodiments of the formulae above, L ⁴ is -CH ₂ CH ₂ P(O)(CH ₃ )-. [00196] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ⁴ , R ^4a , and R ^4b ) are applicable to compounds of Formulae (I), (I-2), (I-3), (I-4), (I-5), (I-6) and (I-1), or a pharmaceutically acceptable salt or solvate thereof. [00197] In embodiments of the formulae above, R ⁴ is wherein each W ¹¹ and W ¹³ are independently selected from O, S, CH, CR ^4b , CH ₂ , CHR ^4b , C(R ^4b ) ₂ , N, NH, and NR ^4b and W ¹² is independently selected from C, CH, CR ^4b , and N, wherein at least one of W ¹¹ and W ¹³ is N, NH, or NR ^4b or W ¹² is N, and wherein the ring including W ¹¹ , W ¹² , and W ¹³ is not an aromatic ring. indicates a single or double bond such that all valences are satisfied. It will be understood that when W ¹¹ is N, NH, or N ^4b , then only one, two, or three W ¹¹ may be N, NH, or N ^4b and each W ¹¹ may optionally be different and may each be independently selected from O, S, CH, CR ^4b , CH ₂ , CHR ^4b , C(R ^4b ) ₂ , N, NH, and NR ^4b with the requirement that at least one of W ¹¹ and W ¹³ is N, NH, or NR ^4b , or W ¹² is N. For example, when R ⁴ includes three W ¹¹ , one W ¹¹ may be N, a second W ¹¹ may be CR ^4b , and a third W ¹¹ may be CH ₂ . [00198] In embodiments of the formulae above R ⁴ is selected from -NH ₂ , CN, and -C(O)NH ₂ . In embodiments of the formulae above, R ⁴ is selected from -NH ₂ , CN, -C(O)NH ₂ , -C(O)H, -N(CH ₃ ) ₂ , halogen, -OH, -OCH ₃ , and oxo. [00199] In embodiments of the formulae above, R ⁴ is . In embodiments of the formulae above, R ⁴ is In embodiments of the formu ⁴ lae above, R is In embodiments of the formulae above, R ⁴ is I ⁴ n embodiments of the formulae above, R is In embodiments of the formulae above, R ⁴ is . In embodiments of the formulae above, R ⁴ is selected from In embodiments of the formulae above, R ⁴ is In embodiments of the formulae above, R ⁴ is In embodiments of the formulae above, R ⁴ is In embodiments of the formulae abo ⁴ ve, R is . In embodiments of the formulae above, R ⁴ is In embodiments of the formulae above, R ⁴ is In embodiments of the formulae above, R ⁴ is selected from , , , , , a d . In embodiments of the formulae above, R ⁴ is In embodiments of the formulae above, R ⁴ is In embodiments of the formulae above, R ⁴ is . In embodiments of the formulae above, R ⁴ is In embodiments of the formulae above, R ⁴ is In embodiments of ⁴ the formulae above, R is . [00200] In embodiments of the formulae above, R ⁴ is selected from: , , [00201] In embodiments of the formulae above, R ⁴ is selected from: , , , [00202] In embodiments of the formulae above, R ⁴ is selected from: [00203] In embodiments of the formulae above, R ⁴ is selected from: [00204] In embodiments of the formulae above, R ⁴ is selected from:

[00205] In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid moiety. In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a Ras protein. In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a K-Ras protein. In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a mutant K-Ras protein. In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant K-Ras protein. In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant G12D K-Ras protein. In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant K-Ras protein. In embodiments of the formulae above, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant G13D K-Ras protein. [00206] In embodiments of the formulae above, R ⁴ is capable of forming a covalent bond with the 12 ^th amino acid of a G12D KRas mutant. In embodiments of the formulae above, R ⁴ is capable of forming a covalent bond with the 12 ^th amino acid of a G12C KRas mutant. In embodiments of the formulae above, R ⁴ is capable of forming a covalent bond with the 12 ^th amino acid of a G12S KRas mutant. In embodiments of the formulae above, R ⁴ is capable of forming a covalent bond with the 13 ^th amino acid of a G13D KRas mutant. In embodiments of the formulae above, R ⁴ is capable of forming a covalent bond with the 13 ^th amino acid of a G13C KRas mutant. In embodiments of the formulae above, R ⁴ is capable of forming a covalent bond with the 13 ^th amino acid of a G13S KRas mutant. [00207] In embodiments of the formulae above, R ^4a is 3 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with one, two, or three R ^4b . In embodiments of the formulae above, R ^4a is 3 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with C _1-6 alkyl optionally substituted with one, two, or three halogen. In embodiments of the formulae above, R ^4a is 3 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with C _1-6 alkyl optionally substituted with one, two, or three F. In embodiments of the formulae above, R ^4a is 3 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with one, two, or three R ^4b . In embodiments of the formulae above, R ^4a is 3 membered heterocycloalkyl comprising one ring nitrogen atom, substituted with Cl and optionally substituted with one, two, or three R ^4b . In embodiments of the formulae above, R ^4a is an unsubstituted 3 membered heterocycloalkyl comprising one ring nitrogen atom. In embodiments of the formulae above, R ^4a is 3 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with C _3-4 cycloalkyl. [00208] In embodiments of the formulae above, R ^4a is 4 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with one, two, or three R ^4b . In embodiments of the formulae above, R ^4a is 4 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with C _1-6 alkyl optionally substituted with one, two, or three halogen. In embodiments of the formulae above, R ^4a is 4 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with C _1-6 alkyl optionally substituted with one, two, or three F. In embodiments of the formulae above, R ^4a is 4 membered heterocycloalkyl comprising one ring nitrogen atom, optionally substituted with one, two, or three R ^4b . In embodiments of the formulae above, R ^4a is 4 membered heterocycloalkyl comprising one ring nitrogen atom, substituted with Cl and optionally substituted with one, two, or three R ^4b . [00209] In embodiments of the formulae above, R ⁴ is selected from [00210] In embodiments of the formulae above, R ^4a is selected from

[00211] In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, ^4a R is In embodiments of the formulae ab ^4a ove, R is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is ^4a In embodiments of the formulae above, R is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the fo ^4a rmulae above, R is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodime ^4a nts of the formulae above, R is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In ^4a embodiments of the formulae above, R is . In embodiments of the formulae above, R ^4a is In embodiments of the fo ^4a rmulae above, R is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the f ^4a ormulae above, R is In embodiments of the formulae above, R ^4a i . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae abo ^4a ve, R is In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments o ^4a f the formulae above, R is In embodiments of the formulae above, R ^4a is ^4a In embodiments of the formulae above, R is . In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is [00212] In embodiments of the formulae above, R ^4a is selected from , , [00213] In embodiments of the formulae above, R ^4a is selected from

[00214] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different. [00215] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different. [00216] In embodiments of the formulae above, R ^4a is selected from wherein e ^4b ach R is independently selected and are optionally different. [00217] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different. [00218] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different. [00219] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different. [00220] In embodiments of the formulae above, R ^4a is selected from: and [00221] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different, [00222] In embodiments of the formulae above, R ^4a is selected from independently selected and are optionally different. [00223] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different. [00224] In embodiments of the formulae above, R ^4a is selected from wherein each R ^4b is independently selected and are optionally different. [00225] In embodiments of the formulae above, R ^4a is selected from and . In embodiments of the formulae above, R ^4a is . In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is In embodiments of the formulae above, R ^4a is [00226] In embodiments of the formulae above, R ^4a is [00227] In embodiments of the formulae above, R ^4a is bonded to L ⁴ through a ring nitrogen atom of R ^4a . In embodiments of the formulae above, R ^4a is bonded to L ⁴ through a ring carbon atom of R ^4a . [00228] In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid moiety. In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a Ras protein. In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a K-Ras protein. In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a mutant K-Ras protein. In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant K-Ras protein. In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant G12D K-Ras protein. In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant K-Ras protein. In embodiments of the formulae above, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant G13D K-Ras protein. [00229] In embodiments of the formulae above, R ^4a is independently selected from [00230] In embodiments of the formulae above, R ^4b is independently selected from halogen, oxo, -CN, C _1-3 alkyl, C _3-4 cycloalkyl, C _2-3 heterocycloalkyl, phenyl, C _1-4 heteroaryl, -OH, -SH, -NH ₂ , -C(O)OCH ₃ , -OC(O)NH ₂ , -C(O)CH ₃ , -S(O)CH ₃ , -OC(O)CH ₃ , -C(O)NH ₂ , -NHC(O)CH ₃ , -S(O) ₂ CH ₃ , and -S(O) ₂ NH ₂ , wherein C _1-3 alkyl, C _2-3 alkenyl, C ₂ - 3alkynyl, C _3-4 cycloalkyl, C _2-3 heterocycloalkyl, phenyl, and C _1-4 heteroaryl are optionally substituted with one or more R ^20h . [00231] In embodiments of the formulae above, each R ^4b is independently selected from halogen, oxo, -CN, C _{1- 3} alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-4 cycloalkyl, C _2-3 heterocycloalkyl, phenyl, C _1-4 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , - S(O) ₂ R ¹⁵ , and -S(O) ₂ N(R ¹² )(R ¹³ ), and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _{3- 4} cycloalkyl, C _2-3 heterocycloalkyl, phenyl, and C _1-4 heteroaryl are optionally substituted with one or more R ^20h . [00232] In embodiments of the formulae above, each R ^4b is independently selected from halogen, -CN, C _1-3 alkyl, C _3-4 cycloalkyl, C _2-3 heterocycloalkyl, phenyl, C _1-4 heteroaryl, -OH, -SH, -NH ₂ , -C(O)OCH ₃ , -OC(O)NH ₂ , -C(O)CH ₃ , -S(O)CH ₃ , -OC(O)CH ₃ , -C(O)NH ₂ , -NHC(O)CH ₃ , -S(O) ₂ CH ₃ , and -S(O) ₂ NH ₂ , wherein C _1-3 alkyl, C _2-3 alkenyl, C _{2- 3} alkynyl, C _3-4 cycloalkyl, C _2-3 heterocycloalkyl, phenyl, and C _1-4 heteroaryl are optionally substituted with one or more R ^20h . [00233] In embodiments of the formulae above, each R ^4b is independently a C ₁ alkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₂ alkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₃ alkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₄ alkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₅ alkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₆ alkyl optionally substituted with one, two, or three R ^20h . [00234] In embodiments of the formulae above, each R ^4b is independently a C ₂ alkenyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₃ alkenyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₄ alkenyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₅ alkenyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₆ alkenyl optionally substituted with one, two, or three R ^20h . [00235] In embodiments of the formulae above, each R ^4b is independently a C ₂ alkynyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₃ alkynyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₄ alkynyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C5alkynyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₆ alkynyl optionally substituted with one, two, or three R ^20h . [00236] In embodiments of the formulae above, each R ^4b is independently a C ₃ heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₄ heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₅ heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₆ heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₇ heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C8heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₉ heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₁₀ heterocycloalkyl optionally substituted with one, two, or three R ^20h . [00237] In embodiments of the formulae above, each R ^4b is independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, 5-10 membered heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , - S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl are optionally substituted with one or more R ^20h ; [00238] In embodiments of the formulae above, each R ^4b is independently a C ₃ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₄ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₅ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₆ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₇ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₈ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₉ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₁₀ cycloalkyl optionally substituted with one, two, or three R ^20h . [00239] In embodiments of the formulae above, each R ^4b is independently a 3 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 4 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 5 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 6 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 7 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 8 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 9 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 10 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . [00240] In embodiments of the formulae above, each R ^4b is independently a C ₆ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₆ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C7aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₈ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₉ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a C ₁₀ aryl optionally substituted with one, two, or three R ^20h . [00241] In embodiments of the formulae above, each R ^4b is independently a 5 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 6 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 7 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 8 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 9 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a 10 membered heteroaryl optionally substituted with one, two, or three R ^20h . [00242] In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₃ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₄ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₅ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₆ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₇ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₈ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₉ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₁₀ cycloalkyl optionally substituted with one, two, or three R ^20h . [00243] In embodiments of the formulae above, each R ^4b is independently a monocyclic 3 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 4 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 5 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 6 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 7 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 8 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 9 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 10 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . [00244] In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₆ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic C ₆ aryl. [00245] In embodiments of the formulae above, each R ^4b is independently a monocyclic 5 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a monocyclic 6 membered heteroaryl optionally substituted with one, two, or three R ^20h . [00246] In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₄ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₅ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₆ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₇ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₈ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₉ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₁₀ cycloalkyl optionally substituted with one, two, or three R ^20h . [00247] In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 4 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 5 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 6 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 7 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 8 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 9 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 10 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . [00248] In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₇ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₈ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C9aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic C ₁₀ aryl optionally substituted with one, two, or three R ^20h . [00249] In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 7 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 8 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 9 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a fused bicyclic 10 membered heteroaryl optionally substituted with one, two, or three R ^20h . [00250] In embodiments of the formulae above, each R ^4b is independently a spirocyclic C5cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic C ₆ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic C ₇ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic C ₈ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic C ₉ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic C ₁₀ cycloalkyl optionally substituted with one, two, or three R ^20h . [00251] In embodiments of the formulae above, each R ^4b is independently a spirocyclic 5 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic 6 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic 7 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic 8 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic 9 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a spirocyclic 10 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . [00252] In embodiments of the formulae above, each R ^4b is independently a bridged C5cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₆ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₇ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₈ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₉ cycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₁₀ cycloalkyl optionally substituted with one, two, or three R ^20h . [00253] In embodiments of the formulae above, each R ^4b is independently a bridged 5 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 6 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 7 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 8 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 9 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 10 membered heterocycloalkyl optionally substituted with one, two, or three R ^20h . [00254] In embodiments of the formulae above, each R ^4b is independently a bridged C ₇ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₈ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₉ aryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged C ₁₀ aryl optionally substituted with one, two, or three R ^20h . [00255] In embodiments of the formulae above, each R ^4b is independently a bridged 6 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 7 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 8 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 9 membered heteroaryl optionally substituted with one, two, or three R ^20h . In embodiments of the formulae above, each R ^4b is independently a bridged 10 membered heteroaryl optionally substituted with one, two, or three R ^20h . [00256] In embodiments of the formulae above, each R ^4b is independently a halogen. In embodiments of the formulae above, each R ^4b is independently a -CN. In embodiments of the formulae above, each R ^4b is independently a -OR ¹² . In embodiments of the formulae above, each R ^4b is independently a -SR ¹² . In embodiments of the formulae above, each R ^4b is independently a -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, each R ^4b is independently a -C(O)OR ¹² . In embodiments of the formulae above, each R ^4b is independently a - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, each R ^4b is independently a -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, each R ^4b is independently a -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -C(O)R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -S(O)R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -OC(O)R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, each R ^4b is independently a -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, each R ^4b is independently a - N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -S(O) ₂ N(R ¹² )(R ¹³ )- . In embodiments of the formulae above, each R ^4b is independently a S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, each R ^4b is independently a -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, each R ^4b is independently a -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, each R ^4b is independently a -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). [00257] In embodiments of the formulae above, each R ^4b is independently a halogen. In embodiments of the formulae above, each R ^4b is independently a -CN. In embodiments of the formulae above, each R ^4b is independently a -OH. In embodiments of the formulae above, each R ^4b is independently a -SH. In embodiments of the formulae above, each R ^4b is independently a -NH ₂ . In embodiments of the formulae above, each R ^4b is independently a -C(O)OH. In embodiments of the formulae above, each R ^4b is independently a -C(O)OCH ₂ CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -OC(O)NH ₂ . In embodiments of the formulae above, each R ^4b is independently a -N(H)C(O)NH ₂ . In embodiments of the formulae above, each R ^4b is independently a -N(H)C(O)OH. In embodiments of the formulae above, each R ^4b is independently a - N(H)S(O) ₂ CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -C(O)CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -S(O)CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -OC(O)CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -C(O)NH ₂ . In embodiments of the formulae above, each R ^4b is independently a -C(O)C(O)NH ₂ . In embodiments of the formulae above, each R ^4b is independently a -N(H)C(O)CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -S(O) ₂ CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ^4b is independently a S(=O)(=NH)NH ₂ . In embodiments of the formulae above, each R ^4b is independently a -CH ₂ C(O)NH ₂ . In embodiments of the formulae above, each R ^4b is independently a -CH ₂ N(H)C(O)CH ₃ . In embodiments of the formulae above, each R ^4b is independently a - CH ₂ S(O) ₂ CH ₃ . In embodiments of the formulae above, each R ^4b is independently a -CH ₂ S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ^4b is independently oxo. In embodiments of the formulae above, each R ^4b is independently -P(=O)(R ¹² ) ₂ . In embodiments of the formulae above, each R ^4b is independently -P(=O)(CH ₃ ) ₂ . In embodiments of the formulae above, each R ^4b is independently a -F. In embodiments of the formulae above, each R ^4b is independently a -Cl. In embodiments of the formulae above, each R ^4b is independently a -I. In embodiments of the formulae above, each R ^4b is independently a -Br. [00258] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^4c or R ^4d ) are applicable to compounds of Formulae (I), (I-2), (I-3), (I-4), (I-5), (I-6), (I-1), (II), and (II-1), or a pharmaceutically acceptable salt or solvate thereof. [00259] In embodiments of the formulae above, R ^4c is independently hydrogen. In embodiments of the formulae above, R ^4c is independently halogen. In embodiments of the formulae above, R ^4c is independently -CN. In embodiments of the formulae above, R ^4c is independently C _1-6 alkyl. In embodiments of the formulae above, R ^4c is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^4c is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^4c is independently C _1-6 haloalkyl. In embodiments of the formulae above, R ^4c is independently C _1-6 alkoxy. In embodiments of the formulae above, R ^4c is independently C _1-6 haloalkoxy. In embodiments of the formulae above, R ^4c is independently C _3-10 cycloalkyl. In embodiments of the formulae above, R ^4c is independently -CH ₂ -C _3-10 cycloalkyl. In embodiments of the formulae above, R ^4c is independently C ₂ - ₉ heterocycloalkyl. In embodiments of the formulae above, R ^4c is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^4c is independently -OR ¹⁴ . In embodiments of the formulae above, R ^4c is independently -SR ¹⁴ . In embodiments of the formulae above, R ^4c is independently -C(O)OR ¹⁴ . In embodiments of the formulae above, R ^4c is independently -C(O)N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4c is independently -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4c is independently - OC(O)N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4c is independently -C(O)R ^14a . In embodiments of the formulae above, R ^4c is independently -S(O) ₂ R ¹⁴ . In embodiments of the formulae above, R ^4c is independently - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4c is independently -OCH ₂ C(O)OR ¹⁴ . In embodiments of the formulae above, R ^4c is independently -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently -N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4c is independently -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4c is independently -N(R ¹⁴ )C(O)OR ¹⁴ . In embodiments of the formulae above, R ^4c is independently -N(R ¹⁴ )C(O)R ^14a . In embodiments of the formulae above, R ^4c is independently - N(R ¹⁴ )S(O) ₂ R ¹⁴ . [00260] In embodiments of the formulae above, R ^4c is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , - C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , - N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently C _1-6 haloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , - N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently C _1-6 alkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently C _1-6 haloalkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4c is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . [00261] In embodiments of the formulae above, R ^4d is independently hydrogen. In embodiments of the formulae above, R ^4d is independently -CN. In embodiments of the formulae above, R ^4d is independently C _1-6 alkyl. In embodiments of the formulae above, R ^4d is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^4d is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^4d is independently C _1-6 haloalkyl. In embodiments of the formulae above, R ^4d is independently C _1-6 alkoxy. In embodiments of the formulae above, R ^4d is independently C _1-6 haloalkoxy. In embodiments of the formulae above, R ^4d is independently C _3-10 cycloalkyl. In embodiments of the formulae above, R ^4d is independently -CH ₂ -C _3-10 cycloalkyl. In embodiments of the formulae above, R ^4d is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^4d is independently - CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^4d is independently -OR ¹⁴ . In embodiments of the formulae above, R ^4d is independently -SR ¹⁴ . In embodiments of the formulae above, R ^4d is independently - C(O)OR ¹⁴ . In embodiments of the formulae above, R ^4d is independently -C(O)N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4d is independently -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4d is independently -OC(O)N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4d is independently -C(O)R ^14a . In embodiments of the formulae above, R ^4d is independently -S(O) ₂ R ¹⁴ . In embodiments of the formulae above, R ^4d is independently -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ). In embodiments of the formulae above, R ^4d is independently -OCH ₂ C(O)OR ¹⁴ . In embodiments of the formulae above, R ^4d is independently -OC(O)R ^14a . [00262] In embodiments of the formulae above, R ^4d is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , - C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , - N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently C _1-6 haloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , - N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently C _1-6 alkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently C _1-6 haloalkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^4d is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . [00263] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ⁵ , R ^5a , or R ^5b ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00264] In embodiments of the formulae above, R ⁵ is hydrogen. In embodiments of the formulae above, R ⁵ is halogen. In embodiments of the formulae above, R ⁵ is -CN. In embodiments of the formulae above, R ⁵ is C _1-6 alkyl. In embodiments of the formulae above, R ⁵ is C _2-6 alkenyl. In embodiments of the formulae above, R ⁵ is C _2-6 alkynyl. In embodiments of the formulae above, R ⁵ is C _3-10 cycloalkyl. In embodiments of the formulae above, R ⁵ is C ₂ - ₉ heterocycloalkyl. In embodiments of the formulae above, R ⁵ is C _6-10 aryl. In embodiments of the formulae above, R ⁵ is C _1-9 heteroaryl. [00265] In embodiments of the formulae above, R ⁵ is C _1-6 alkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ⁵ is C _2-6 alkenyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ⁵ is C _2-6 alkynyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ⁵ is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ⁵ is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ⁵ is C _6-10 aryl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ⁵ is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20c . [00266] In embodiments of the formulae above, R ⁵ is -OR ¹² . In embodiments of the formulae above, R ⁵ is -SR ¹² . In embodiments of the formulae above, R ⁵ is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is -C(O)OR ¹² . In embodiments of the formulae above, R ⁵ is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ⁵ is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁵ is -C(O)R ¹⁵ . In embodiments of the formulae above, R ⁵ is -S(O)R ¹⁵ . In embodiments of the formulae above, R ⁵ is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ⁵ is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ⁵ is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁵ is -S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁵ is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ⁵ is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁵ is -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ⁵ is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00267] In embodiments of the formulae above, R ^5a is hydrogen. In embodiments of the formulae above, R ^5a is halogen. In embodiments of the formulae above, R ^5a is -CN. In embodiments of the formulae above, R ^5a is C _1-6 alkyl. In embodiments of the formulae above, R ^5a is C _2-6 alkenyl. In embodiments of the formulae above, R ^5a is C _{2- 6} alkynyl. In embodiments of the formulae above, R ^5a is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^5a is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^5a is C _6-10 aryl. In embodiments of the formulae above, R ^5a is C _1-9 heteroaryl. [00268] In embodiments of the formulae above, R ^5a is C _1-6 alkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5a is C _2-6 alkenyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5a is C _2-6 alkynyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5a is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5a is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5a is C _6-10 aryl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5a is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20c . [00269] In embodiments of the formulae above, R ^5a is -OR ¹² . In embodiments of the formulae above, R ^5a is -SR ¹² . In embodiments of the formulae above, R ^5a is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is - C(O)OR ¹² . In embodiments of the formulae above, R ^5a is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ^5a is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^5a is - C(O)R ¹⁵ . In embodiments of the formulae above, R ^5a is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^5a is - OC(O)R ¹⁵ . In embodiments of the formulae above, R ^5a is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^5a is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^5a is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5a is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^5a is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^5a is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^5a is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00270] In embodiments of the formulae above, R ^5b is hydrogen. In embodiments of the formulae above, R ^5b is halogen. In embodiments of the formulae above, R ^5b is -CN. In embodiments of the formulae above, R ^5b is C _{1- 6} alkyl. In embodiments of the formulae above, R ^5b is C _2-6 alkenyl. In embodiments of the formulae above, R ^5b is C _{2- 6} alkynyl. In embodiments of the formulae above, R ^5b is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^5b is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^5b is C _6-10 aryl. In embodiments of the formulae above, R ^5b is C _1-9 heteroaryl. [00271] In embodiments of the formulae above, R ^5b is C _1-6 alkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5b is C _2-6 alkenyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5b is C _2-6 alkynyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5b is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5b is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5b is C _6-10 aryl optionally substituted with one, two, or three R ^20c . In embodiments of the formulae above, R ^5b is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20c . [00272] In embodiments of the formulae above, R ^5b is -OR ¹² . In embodiments of the formulae above, R ^5b is -SR ¹² . In embodiments of the formulae above, R ^5b is -C(O)OR ¹² . In embodiments of the formulae above, R ^5b is - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5b is -C(O)R ¹⁵ . In embodiments of the formulae above, R ^5b is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^5b is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^5b is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5b is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5b is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^5b is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5b is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5b is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^5b is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^5b is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^5b is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^5b is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00273] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ⁶ , R ^6a , or R ^6b ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00274] In embodiments of the formulae above, R ⁶ is hydrogen. In embodiments of the formulae above, R ⁶ is halogen. In embodiments of the formulae above, R ⁶ is -CN. In embodiments of the formulae above, R ⁶ is C _1-6 alkyl. In embodiments of the formulae above, R ⁶ is C _2-6 alkenyl. In embodiments of the formulae above, R ⁶ is C _2-6 alkynyl. In embodiments of the formulae above, R ⁶ is C _3-10 cycloalkyl. In embodiments of the formulae above, R ⁶ is C _{2- 9} heterocycloalkyl. In embodiments of the formulae above, R ⁶ is C _6-10 aryl. In embodiments of the formulae above, R ⁶ is C _1-9 heteroaryl. In embodiments of the formulae above, R ⁶ is F. In embodiments of the formulae above, R ⁶ is Cl. In embodiments of the formulae above, R ⁶ is Br. In embodiments of the formulae above, R ⁶ is I. In embodiments of the formulae above, R ⁶ is cyclopropyl. In embodiments of the formulae above, R ⁶ is CN substituted C _1-4 alkyl. In embodiments of the formulae above, R ⁶ is CN substituted propyl. In embodiments of the formulae above, R ⁶ is CN substituted ethyl. In embodiments of the formulae above, R ⁶ is CN substituted butyl. In embodiments of the formulae above, R ⁶ is CN substituted methyl. [00275] In embodiments of the formulae above, R ⁶ is C _1-6 alkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ⁶ is C _2-6 alkenyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ⁶ is C _2-6 alkynyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ⁶ is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ⁶ is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ⁶ is C _6-10 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ⁶ is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20d . [00276] In embodiments of the formulae above, R ⁶ is -OR ¹² . In embodiments of the formulae above, R ⁶ is -SR ¹² . In embodiments of the formulae above, R ⁶ is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is -C(O)OR ¹² . In embodiments of the formulae above, R ⁶ is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ⁶ is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁶ is -C(O)R ¹⁵ . In embodiments of the formulae above, R ⁶ is -S(O)R ¹⁵ . In embodiments of the formulae above, R ⁶ is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ⁶ is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ⁶ is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁶ is -S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁶ is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ⁶ is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁶ is -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ⁶ is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00277] In embodiments of the formulae above, R ^6a is hydrogen. In embodiments of the formulae above, R ^6a is halogen. In embodiments of the formulae above, R ^6a is -CN. In embodiments of the formulae above, R ^6a is C _1-6 alkyl. In embodiments of the formulae above, R ^6a is C _2-6 alkenyl. In embodiments of the formulae above, R ^6a is C ₂ - ₆ alkynyl. In embodiments of the formulae above, R ^6a is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^6a is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^6a is C _6-10 aryl. In embodiments of the formulae above, R ^6a is C _1-9 heteroaryl. [00278] In embodiments of the formulae above, R ^6a is C _1-6 alkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6a is C _2-6 alkenyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6a is C _2-6 alkynyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6a is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6a is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6a is C _6-10 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6a is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20d . [00279] In embodiments of the formulae above, R ^6a is -OR ¹² . In embodiments of the formulae above, R ^6a is -SR ¹² . In embodiments of the formulae above, R ^6a is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is - C(O)OR ¹² . In embodiments of the formulae above, R ^6a is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ^6a is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^6a is - C(O)R ¹⁵ . In embodiments of the formulae above, R ^6a is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^6a is - OC(O)R ¹⁵ . In embodiments of the formulae above, R ^6a is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^6a is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^6a is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6a is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^6a is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^6a is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^6a is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00280] In embodiments of the formulae above, R ^6b is hydrogen. In embodiments of the formulae above, R ^6b is halogen. In embodiments of the formulae above, R ^6b is -CN. In embodiments of the formulae above, R ^6b is C _{1- 6} alkyl. In embodiments of the formulae above, R ^6b is C _2-6 alkenyl. In embodiments of the formulae above, R ^6b is C ₂ - ₆ alkynyl. In embodiments of the formulae above, R ^6b is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^6b is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^6b is C _6-10 aryl. In embodiments of the formulae above, R ^6b is C _1-9 heteroaryl. [00281] In embodiments of the formulae above, R ^6b is C _1-6 alkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6b is C _2-6 alkenyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6b is C _2-6 alkynyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6b is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6b is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6b is C _6-10 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ^6b is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20d . [00282] In embodiments of the formulae above, R ^6b is -OR ¹² . In embodiments of the formulae above, R ^6b is -SR ¹² . In embodiments of the formulae above, R ^6b is -C(O)OR ¹² . In embodiments of the formulae above, R ^6b is - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6b is -C(O)R ¹⁵ . In embodiments of the formulae above, R ^6b is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^6b is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^6b is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6b is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6b is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^6b is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6b is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6b is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^6b is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^6b is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^6b is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^6b is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00283] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of L ⁷ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00284] In embodiments of the formulae above, L ⁷ is a bond. In embodiments of the formulae above, L ⁷ is -O-. In embodiments of the formulae above, L ⁷ is -N(R ^7d )-. In embodiments of the formulae above, L ⁷ is -C(O)- . In embodiments of the formulae above, L ⁷ is -S-. In embodiments of the formulae above, L ⁷ is -S(O) ₂ -. In embodiments of the formulae above, L ⁷ is -S(O)- . In embodiments of the formulae above, L ⁷ is -P(O)R ^7d -. In embodiments of the formulae above, L ⁷ is CR ^7c R ^7c . In embodiments of the formulae above, L ⁷ is -OCR ^7c R ^7c -. In embodiments of the formulae above, L ⁷ is -N(R ^7d )CR ^7c R ^7c -. In embodiments of the formulae above, L ⁷ is - C(O)CR ^7c R ^7c -. In embodiments of the formulae above, L ⁷ is -SCR ^7c R ^7c -. In embodiments of the formulae above, L ⁷ is -S(O) ₂ CR ^7c R ^7c -. In embodiments of the formulae above, L ⁷ is -S(O)CR ^7c R ^7c -. In embodiments of the formulae above, L ⁷ is -P(O)R ^7d CR ^7c R ^7c -. In embodiments of the formulae above, L ⁷ is -CR ^7c R ^7c CR ^7c R ^7c . In embodiments of the formulae above, L ⁷ is -CR ^7c R ^7c O-. In embodiments of the formulae above, L ⁷ is -CR ^7c R ^7c N(R ^7d )-. In embodiments of the formulae above, L ⁷ is -CR ^7c R ^7c C(O)-. In embodiments of the formulae above, L ⁷ is -CR ^7c R ^7c S-. In embodiments of the formulae above, L ⁷ is -CR ^7c R ^7c S(O) ₂ -. In embodiments of the formulae above, L ⁷ is - CR ^7c R ^7c S(O)-. In embodiments of the formulae above, L ⁷ is -CR ^7c R ^7c P(O)R ^7d -. In embodiments of the formulae above, L ⁷ is -N(R ^7d )C(O)- . In embodiments of the formulae above, L ⁷ is -N(R ^7d )S(O) ₂ -. In embodiments of the formulae above, L ⁷ is -N(R ^7d )S(O)-. In embodiments of the formulae above, L ⁷ is -N(R ^7d )P(O)R ^7d -. In embodiments of the formulae above, L ⁷ is -C(O)N(R ^7d )-. In embodiments of the formulae above, L ⁷ is - S(O) ₂ N(R ^7d )-. In embodiments of the formulae above, L ⁷ is -S(O)N(R ^7d )-. In embodiments of the formulae above, L ⁷ is -P(O)R ^7d N(R ^7d )-. In embodiments of the formulae above, L ⁷ is -OC(O)-. In embodiments of the formulae above, L ⁷ is -OS(O) ₂ -. In embodiments of the formulae above, L ⁷ is -OS(O)- . In embodiments of the formulae above, L ⁷ is -OP(O)R ^7d -. In embodiments of the formulae above, L ⁷ is -C(O)O-. In embodiments of the formulae above, L ⁷ is -S(O) ₂ O-. In embodiments of the formulae above, L ⁷ is -S(O)O-. In embodiments of the formulae above, L ⁷ is -P(O)R ^7d O-. [00285] In embodiments of the formulae above, L ⁷ is a bond. In embodiments of the formulae above, L ⁷ is -O-. In embodiments of the formulae above, L ⁷ is -NH- . In embodiments of the formulae above, L ⁷ is -C(O)- . In embodiments of the formulae above, L ⁷ is -S-. In embodiments of the formulae above, L ⁷ is -S(O) ₂ -. In embodiments of the formulae above, L ⁷ is -S(O)- . In embodiments of the formulae above, L ⁷ is -P(O)CH ₃ -. In embodiments of the formulae above, L ⁷ is CH ₂ . In embodiments of the formulae above, L ⁷ is -OCH ₂ -. In embodiments of the formulae above, L ⁷ is -N(H)CH ₂ -. In embodiments of the formulae above, L ⁷ is -C(O)CH ₂ -. In embodiments of the formulae above, L ⁷ is -SCH ₂ -. In embodiments of the formulae above, L ⁷ is -S(O) ₂ CH ₂ -. In embodiments of the formulae above, L ⁷ is -S(O)CH ₂ -. In embodiments of the formulae above, L ⁷ is - P(O)(CH ₃ )CH ₂ -. In embodiments of the formulae above, L ⁷ is -CH ₂ CH ₂ . In embodiments of the formulae above, L ⁷ is -CH ₂ O-. In embodiments of the formulae above, L ⁷ is -CH ₂ N(H)- . In embodiments of the formulae above, L ⁷ is -CH ₂ C(O)- . In embodiments of the formulae above, L ⁷ is -CH ₂ S-. In embodiments of the formulae above, L ⁷ is - CH ₂ S(O) ₂ -. In embodiments of the formulae above, L ⁷ is -CH ₂ S(O)- . In embodiments of the formulae above, L ⁷ is -CH ₂ P(O)CH ₃ -. In embodiments of the formulae above, L ⁷ is -N(H)C(O)- . In embodiments of the formulae above, L ⁷ is -N(H)S(O) ₂ -. In embodiments of the formulae above, L ⁷ is -N(H)S(O)- . In embodiments of the formulae above, L ⁷ is -N(H)P(O)CH ₃ -. In embodiments of the formulae above, L ⁷ is -C(O)N(H)- . In embodiments of the formulae above, L ⁷ is -S(O) ₂ N(H)- . In embodiments of the formulae above, L ⁷ is -S(O)N(H)- . In embodiments of the formulae above, L ⁷ is -P(O)(CH ₃ )N(H)- . In embodiments of the formulae above, L ⁷ is -OC(O)- . In embodiments of the formulae above, L ⁷ is -OS(O) ₂ -. In embodiments of the formulae above, L ⁷ is -OS(O)- . In embodiments of the formulae above, L ⁷ is -OP(O)CH ₃ -. In embodiments of the formulae above, L ⁷ is -C(O)O-. In embodiments of the formulae above, L ⁷ is -S(O) ₂ O-. In embodiments of the formulae above, L ⁷ is -S(O)O-. In embodiments of the formulae above, L ⁷ is -P(O)(CH ₃ )O-. [00286] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^7a , R ^7c , or R ^7d ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00287] In embodiments of the formulae above, R ^7a is hydrogen. In embodiments of the formulae above, R ^7a is halogen. In embodiments of the formulae above, R ^7a is -CN. In embodiments of the formulae above, R ^7a is C _1-6 alkyl. In embodiments of the formulae above, R ^7a is C _2-6 alkenyl. In embodiments of the formulae above, R ^7a is C ₂ - ₆ alkynyl. In embodiments of the formulae above, R ^7a is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^7a is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^7a is C _6-10 aryl. In embodiments of the formulae above, R ^7a is C _1-9 heteroaryl. [00288] In embodiments of the formulae above, R ^7a is C _1-6 alkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7a is C _2-6 alkenyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7a is C _2-6 alkynyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7a is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7a is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7a is C _6-10 aryl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7a is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20e . [00289] In embodiments of the formulae above, R ^7a is -OR ¹² . In embodiments of the formulae above, R ^7a is -SR ¹² . In embodiments of the formulae above, R ^7a is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is - C(O)OR ¹² . In embodiments of the formulae above, R ^7a is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ^7a is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7a is - C(O)R ¹⁵ . In embodiments of the formulae above, R ^7a is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^7a is - OC(O)R ¹⁵ . In embodiments of the formulae above, R ^7a is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^7a is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7a is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7a is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^7a is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7a is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^7a is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00290] In embodiments of the formulae above, R ^7c is hydrogen. In embodiments of the formulae above, R ^7c is halogen. In embodiments of the formulae above, R ^7c is -CN. In embodiments of the formulae above, R ^7c is C _1-6 alkyl. In embodiments of the formulae above, R ^7c is C _2-6 alkenyl. In embodiments of the formulae above, R ^7c is C _{2- 6} alkynyl. In embodiments of the formulae above, R ^7c is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^7c is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^7c is C _6-10 aryl. In embodiments of the formulae above, R ^7c is C _1-9 heteroaryl. [00291] In embodiments of the formulae above, R ^7c is C _1-6 alkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7c is C _2-6 alkenyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7c is C _2-6 alkynyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7c is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7c is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7c is C _6-10 aryl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7c is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20e . [00292] In embodiments of the formulae above, R ^7c is -OR ¹² . In embodiments of the formulae above, R ^7c is -SR ¹² . In embodiments of the formulae above, R ^7c is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is - C(O)OR ¹² . In embodiments of the formulae above, R ^7c is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ^7c is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7c is - C(O)R ¹⁵ . In embodiments of the formulae above, R ^7c is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^7c is - OC(O)R ¹⁵ . In embodiments of the formulae above, R ^7c is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^7c is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7c is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7c is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^7c is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7c is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^7c is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00293] In embodiments of the formulae above, R ^7d is hydrogen. In embodiments of the formulae above, R ^7d is halogen. In embodiments of the formulae above, R ^7d is -CN. In embodiments of the formulae above, R ^7d is C _{1- 6} alkyl. In embodiments of the formulae above, R ^7d is C _2-6 alkenyl. In embodiments of the formulae above, R ^7d is C _{2- 6} alkynyl. In embodiments of the formulae above, R ^7d is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^7d is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^7d is C _6-10 aryl. In embodiments of the formulae above, R ^7d is C _1-9 heteroaryl. [00294] In embodiments of the formulae above, R ^7d is C _1-6 alkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7d is C _2-6 alkenyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7d is C _2-6 alkynyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7d is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7d is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7d is C _6-10 aryl optionally substituted with one, two, or three R ^20e . In embodiments of the formulae above, R ^7d is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20e . [00295] In embodiments of the formulae above, R ^7d is -OR ¹² . In embodiments of the formulae above, R ^7d is -SR ¹² . In embodiments of the formulae above, R ^7d is -C(O)OR ¹² . In embodiments of the formulae above, R ^7d is - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7d is -C(O)R ¹⁵ . In embodiments of the formulae above, R ^7d is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^7d is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^7d is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7d is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7d is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7d is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7d is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7d is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^7d is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^7d is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^7d is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^7d is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00296] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ⁸ , R ^8a , or R ^8b ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00297] In embodiments of the formulae above, R ⁸ is hydrogen. In embodiments of the formulae above, R ⁸ is halogen. In embodiments of the formulae above, R ⁸ is -CN. In embodiments of the formulae above, R ⁸ is C _1-6 alkyl. In embodiments of the formulae above, R ⁸ is C _2-6 alkenyl. In embodiments of the formulae above, R ⁸ is C _2-6 alkynyl. In embodiments of the formulae above, R ⁸ is C _3-10 cycloalkyl. In embodiments of the formulae above, R ⁸ is C ₂ - ₉ heterocycloalkyl. In embodiments of the formulae above, R ⁸ is C _6-10 aryl. In embodiments of the formulae above, R ⁸ is C _1-9 heteroaryl. In embodiments of the formulae above, R ⁸ is F. In embodiments of the formulae above, R ⁸ is Cl. In embodiments of the formulae above, R ⁸ is Br. In embodiments of the formulae above, R ⁸ is I. [00298] In embodiments of the formulae above, R ⁸ is C _1-6 alkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ⁸ is C _2-6 alkenyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ⁸ is C _2-6 alkynyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ⁸ is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ⁸ is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ⁸ is C _6-10 aryl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ⁸ is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20f . [00299] In embodiments of the formulae above, R ⁸ is -OR ¹² . In embodiments of the formulae above, R ⁸ is -SR ¹² . In embodiments of the formulae above, R ⁸ is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is -C(O)OR ¹² . In embodiments of the formulae above, R ⁸ is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ⁸ is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁸ is -C(O)R ¹⁵ . In embodiments of the formulae above, R ⁸ is -S(O)R ¹⁵ . In embodiments of the formulae above, R ⁸ is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ⁸ is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ⁸ is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁸ is -S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ⁸ is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ⁸ is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ⁸ is -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ⁸ is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00300] In embodiments of the formulae above, R ^8a is hydrogen. In embodiments of the formulae above, R ^8a is halogen. In embodiments of the formulae above, R ^8a is -CN. In embodiments of the formulae above, R ^8a is C _1-6 alkyl. In embodiments of the formulae above, R ^8a is C _2-6 alkenyl. In embodiments of the formulae above, R ^8a is C _{2- 6} alkynyl. In embodiments of the formulae above, R ^8a is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^8a is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^8a is C _6-10 aryl. In embodiments of the formulae above, R ^8a is C _1-9 heteroaryl. [00301] In embodiments of the formulae above, R ^8a is C _1-6 alkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8a is C _2-6 alkenyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8a is C _2-6 alkynyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8a is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8a is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8a is C _6-10 aryl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8a is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20f . [00302] In embodiments of the formulae above, R ^8a is -OR ¹² . In embodiments of the formulae above, R ^8a is -SR ¹² . In embodiments of the formulae above, R ^8a is -N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is - C(O)OR ¹² . In embodiments of the formulae above, R ^8a is -OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ^8a is -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^8a is - C(O)R ¹⁵ . In embodiments of the formulae above, R ^8a is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^8a is - OC(O)R ¹⁵ . In embodiments of the formulae above, R ^8a is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^8a is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^8a is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8a is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^8a is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^8a is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^8a is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00303] In embodiments of the formulae above, R ^8b is hydrogen. In embodiments of the formulae above, R ^8b is halogen. In embodiments of the formulae above, R ^8b is -CN. In embodiments of the formulae above, R ^8b is C _{1- 6} alkyl. In embodiments of the formulae above, R ^8b is C _2-6 alkenyl. In embodiments of the formulae above, R ^8b is C _{2- 6} alkynyl. In embodiments of the formulae above, R ^8b is C _3-10 cycloalkyl. In embodiments of the formulae above, R ^8b is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^8b is C _6-10 aryl. In embodiments of the formulae above, R ^8b is C _1-9 heteroaryl. [00304] In embodiments of the formulae above, R ^8b is C _1-6 alkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8b is C _2-6 alkenyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8b is C _2-6 alkynyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8b is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8b is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8b is C _6-10 aryl optionally substituted with one, two, or three R ^20f . In embodiments of the formulae above, R ^8b is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20f . [00305] In embodiments of the formulae above, R ^8b is -OR ¹² . In embodiments of the formulae above, R ^8b is -SR ¹² . In embodiments of the formulae above, R ^8b is -C(O)OR ¹² . In embodiments of the formulae above, R ^8b is - OC(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8b is -C(O)R ¹⁵ . In embodiments of the formulae above, R ^8b is -S(O)R ¹⁵ . In embodiments of the formulae above, R ^8b is -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^8b is -C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8b is -C(O)C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8b is -S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^8b is - S(O) ₂ N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8b is S(=O)(=NH)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8b is -CH ₂ C(O)N(R ¹² )(R ¹³ ) . In embodiments of the formulae above, R ^8b is -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^8b is -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^8b is - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^8b is independently -S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). [00306] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ¹⁰ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00307] In embodiments of the formulae above R ¹⁰ is

and p is an integer from 0 to 12. [00308] In embodiments of the formulae above R ¹⁰ is , ,

and p is an integer from 0 to 12. [00309] In embodiments of the formulae above R ¹⁰ is and p is an integer from 0 to 12. [00310] In embodiments of the formulae above R ¹⁰ is ; and p is an integer from 0 to 12. [00311] In some embodiments R ¹⁰ is and p is independently an integer from 0 to 12. [00312] In some embodiments R ¹⁰ is

and p is independently an integer from 0 to 12. [00313] In some embodiments R ¹⁰ is and p is independently an integer from 0 to 12. [00314] In some embodiments R ¹⁰ is , , , , and p is independently an integer from 0 to 12. [00315] In embodiments of the formulae above, R ¹⁰ is selected from ,

[00316] In embodiments of the formulae above, R ¹⁰ is selected from

[00317] In embodiments of the formulae above, R ¹⁰ is selected from [00318] In embodiments of the formulae above, R ¹⁰ is selected from , ,

, , , , , [00319] In embodiments of the formulae above, R ¹⁰ is selected from

In embodiments of the formulae above, R ¹⁰ is selected from and In embodim ¹⁰ ents of the formulae above, R is selected from and . [00320] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of L ¹¹ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00321] In some embodiments of Formulae (I), (I-1), (I-2), (I-3), (I-4), (II), (II-1), (III), and (III-1), L ¹¹ is selected from a bond, -O-, -NH-, -NCH ₃ -, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -S ⁺ (O-)-, -P(O)CH ₃ -, and -CH ₂ -. In some embodiments of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), L ¹¹ is selected from a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -S ⁺ (O-)-, -P(O)CH ₃ -, and -CH ₂ -. [00322] In embodiments of the formulae above, L ¹¹ is a bond. In embodiments of the formulae above, L ¹¹ is -O-. In embodiments of the formulae above, L ¹¹ is -N(R ^11b )-. In embodiments of the formulae above, L ¹¹ is -NH-. In embodiments of the formulae above, L ¹¹ is -NCH ₃ -. In embodiments of the formulae above, L ¹¹ is -C(O)-. In embodiments of the formulae above, L ¹¹ is -S-. In embodiments of the formulae above, L ¹¹ is -S(O) ₂ -. In embodiments of the formulae above, L ¹¹ is -S(O)-. In embodiments of the formulae above, L ¹¹ is -S ⁺ (O-)-. In embodiments of the formulae above, L ¹¹ is -P(O)R ^11b -. In embodiments of the formulae above, L ¹¹ is -P(O)CH ₃ -. In embodiments of the formulae above, L ¹¹ is CR ^11a R ^11a . In embodiments of the formulae above, L ¹¹ is CH ₂ . In embodiments of the formulae above, L ¹¹ is -OCR ^11a R ^11a -. In embodiments of the formulae above, L ¹¹ is - N(R ^11b )CR ^11a R ^11a -. In embodiments of the formulae above, L ¹¹ is -C(O)CR ^11a R ^11a -. In embodiments of the formulae above, L ¹¹ is -SCR ^11a R ^11a -. In embodiments of the formulae above, L ¹¹ is -S(O) ₂ CR ^11a R ^11a -. In embodiments of the formulae above, L ¹¹ is -S(O)CR ^11a R ^11a -. In embodiments of the formulae above, L ¹¹ is -P(O)R ^11b CR ^11a R ^11a -. In embodiments of the formulae above, L ¹¹ is -CR ^11a R ^11a CR ^11a R ^11a . In embodiments of the formulae above, L ¹¹ is - CR ^11a R ^11a O-. In embodiments of the formulae above, L ¹¹ is -CR ^11a R ^11a N(R ^11b )-. In embodiments of the formulae above, L ¹¹ is -CR ^11a R ^11a C(O)-. In embodiments of the formulae above, L ¹¹ is -CR ^11a R ^11a S-. In embodiments of the formulae above, L ¹¹ is -CR ^11a R ^11a S(O) ₂ -. In embodiments of the formulae above, L ¹¹ is -CR ^11a R ^11a S(O)- . In embodiments of the formulae above, L ¹¹ is -CR ^11a R ^11a P(O)R ^11b -. In embodiments of the formulae above, L ¹¹ is - N(R ^11b )C(O)- . In embodiments of the formulae above, L ¹¹ is -N(R ^11b )S(O) ₂ -. In embodiments of the formulae above, L ¹¹ is -N(R ^11b )S(O)- . In embodiments of the formulae above, L ¹¹ is -N(R ^11b )P(O)R ^11b -. In embodiments of the formulae above, L ¹¹ is -C(O)N(R ^11b )-. In embodiments of the formulae above, L ¹¹ is -S(O) ₂ N(R ^11b )-. In embodiments of the formulae above, L ¹¹ is -S(O)N(R ^11b )-. In embodiments of the formulae above, L ¹¹ is - P(O)R ^11b N(R ^11b )-. In embodiments of the formulae above, L ¹¹ is -OC(O)-. In embodiments of the formulae above, L ¹¹ is -OS(O) ₂ -. In embodiments of the formulae above, L ¹¹ is -OS(O)- . In embodiments of the formulae above, L ¹¹ is -OP(O)R ^11b -. In embodiments of the formulae above, L ¹¹ is -C(O)O-. In embodiments of the formulae above, L ¹¹ is -S(O) ₂ O-. In embodiments of the formulae above, L ¹¹ is -S(O)O-. In embodiments of the formulae above, L ¹¹ is -P(O)R ^11b O-. [00323] In embodiments of the formulae above, L ¹¹ is -OCH ₂ -. In embodiments of the formulae above, L ¹¹ is - N(H)CH ₂ -. In embodiments of the formulae above, L ¹¹ is -C(O)CH ₂ -. In embodiments of the formulae above, L ¹¹ is -SCH ₂ -. In embodiments of the formulae above, L ¹¹ is -S(O) ₂ CH ₂ -. In embodiments of the formulae above, L ¹¹ is - S(O)CH ₂ -. In embodiments of the formulae above, L ¹¹ is -P(O)(CH ₃ )CH ₂ -. In embodiments of the formulae above, L ¹¹ is -CH ₂ CH ₂ . In embodiments of the formulae above, L ¹¹ is -CH ₂ O-. In embodiments of the formulae above, L ¹¹ is -CH ₂ N(H)- . In embodiments of the formulae above, L ¹¹ is -CH ₂ C(O)- . In embodiments of the formulae above, L ¹¹ is -CH ₂ S-. In embodiments of the formulae above, L ¹¹ is -CH ₂ S(O) ₂ -. In embodiments of the formulae above, L ¹¹ is -CH ₂ S(O)- . In embodiments of the formulae above, L ¹¹ is -CH ₂ P(O)CH ₃ -. In embodiments of the formulae above, L ¹¹ is -N(H)C(O)- . In embodiments of the formulae above, L ¹¹ is -N(H)S(O) ₂ -. In embodiments of the formulae above, L ¹¹ is -N(H)S(O)- . In embodiments of the formulae above, L ¹¹ is -N(H)P(O)CH ₃ -. In embodiments of the formulae above, L ¹¹ is -C(O)N(H)- . In embodiments of the formulae above, L ¹¹ is -S(O) ₂ N(H)- . In embodiments of the formulae above, L ¹¹ is -S(O)N(H)- . In embodiments of the formulae above, L ¹¹ is - P(O)(CH ₃ )N(H)- . In embodiments of the formulae above, L ¹¹ is -OC(O)- . In embodiments of the formulae above, L ¹¹ is -OS(O) ₂ -. In embodiments of the formulae above, L ¹¹ is -OS(O)- . In embodiments of the formulae above, L ¹¹ is -OP(O)CH ₃ -. In embodiments of the formulae above, L ¹¹ is -C(O)O-. In embodiments of the formulae above, L ¹¹ is -S(O) ₂ O-. In embodiments of the formulae above, L ¹¹ is -S(O)O-. In embodiments of the formulae above, L ¹¹ is -P(O)(CH ₃ )O-. [00324] In embodiments of the formulae above, L ¹¹ is selected from a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, - P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, -C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, - S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , -CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, - CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, -CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)- , -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, -S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, and -P(O)R ^11b O-. [00325] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ¹¹ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00326] In embodiments of the formulae above, R ¹¹ is a 3-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C _6-10 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 5-10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00327] In embodiments of the formulae above, R ¹¹ is a 3-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 4-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 4-7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 6-7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 8-9 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 4-7 membered heterocycloalkyl comprising at least one nitrogen ring atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 6-7 membered heterocycloalkyl comprising at least one nitrogen ring atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 8-9 membered heterocycloalkyl comprising at least one nitrogen ring atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 4-7 membered heterocycloalkyl comprising at least one oxygen ring atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 6-7 membered heterocycloalkyl comprising at least one oxygen ring atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 8-9 membered heterocycloalkyl comprising at least one oxygen ring atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a C _6-10 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a 5-10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00328] In embodiments of the formulae above, R ¹¹ is a C3cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₄ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₅ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₆ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₇ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₈ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₉ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₁₀ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a monocyclic C _4-7 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a spirocyclic carbocyclic bicyclic C _5-10 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a fused carbocyclic bicyclic C _{4- 10} cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a bridged carbocyclic polycyclic C _6-10 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00329] In embodiments of the formulae above, R ¹¹ is a 3 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 4 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 5 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 6 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 8 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 9 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments R ¹¹ is a monocyclic 4-7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a bicyclic 4-10 membered heterocycloalkyl, wherein the bicyclic 4-10 membered heterocycloalkyl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a spirocyclic bicyclic 5-10 membered heterocycloalkyl, wherein spirocyclic bicyclic 5-10 membered heterocycloalkyl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a spirocyclic bicyclic 6-8 membered heterocycloalkyl, wherein the spirocyclic bicyclic 6-8 membered heterocycloalkyl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a fused bicyclic 4-10 membered heterocycloalkyl, wherein the fused bicyclic 4-10 membered heterocycloalkyl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a fused bicyclic 6-8 membered heterocycloalkyl, wherein the fused bicyclic 6-8 membered heterocycloalkyl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a bridged polycyclic 6-10 membered heterocycloalkyl, wherein the bridged polycyclic 6-10 membered heterocycloalkyl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a bridged polycyclic 8-10 membered heterocycloalkyl, wherein the bridged polycyclic 8-10 membered heterocycloalkyl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . In some embodiments, R ¹¹ is a monocyclic 3-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00330] In embodiments of the formulae above, R ¹¹ is a C ₆ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₆ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C7aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₈ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₉ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C ₁₀ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00331] In embodiments of the formulae above, R ¹¹ is a 5 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 6 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 7 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 8 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 9 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00332] In embodiments of the formulae above, R ¹¹ is a monocyclic C ₃ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C ₄ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C5cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C ₆ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C ₇ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C ₈ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C ₉ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C ₁₀ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00333] In embodiments of the formulae above, R ¹¹ is a monocyclic 3 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 4 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 5 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 6 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 8 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 9 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00334] In embodiments of the formulae above, R ¹¹ is a monocyclic C ₆ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . . [00335] In embodiments of the formulae above, R ¹¹ is a monocyclic 5 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 6 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00336] In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₄ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₅ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₆ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₇ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₈ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₉ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₁₀ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00337] In embodiments of the formulae above, R ¹¹ is a fused bicyclic 4 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 5 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 6 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 8 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 9 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 9 membered heterocycloalkyl substituted with one R ⁴ and substituted with one or more R ^11c , wherein one R ^11c and one R ⁴ that are bonded to the same atom are joined to form In embodiments of the formulae above, R ¹¹ is wherein R ¹¹ is substitut ⁴ ed with one R and substituted with one, two, three, or four independent R ^11c , wherein one R ^11c and one R ⁴ that are bonded to the same atom are joined to form In embodiments of the formulae above, R ¹¹ is wherein R ¹¹ is substituted with one R ⁴ and substituted with one R ^11c , wherein one R ^11c and one R ⁴ that are bonded to the same atom are joined to form [00338] In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₇ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C8aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₉ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic C ₁₀ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00339] In embodiments of the formulae above, R ¹¹ is a fused bicyclic 7 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 8 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 9 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a fused bicyclic 10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00340] In embodiments of the formulae above, R ¹¹ is a spirocyclic C ₅ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic C ₆ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic C ₇ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic C ₈ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic C ₉ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic C ₁₀ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00341] In embodiments of the formulae above, R ¹¹ is a spirocyclic 5 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic 6 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic 7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic 8 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic 9 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a spirocyclic 10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00342] In embodiments of the formulae above, R ¹¹ is a bridged C ₅ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C ₆ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C ₇ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C ₈ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C ₉ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C ₁₀ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00343] In embodiments of the formulae above, R ¹¹ is a bridged 5 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 6 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 8 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 9 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00344] In embodiments of the formulae above, R ¹¹ is a bridged C ₇ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C8 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C ₉ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged C ₁₀ aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00345] In embodiments of the formulae above, R ¹¹ is a bridged 6 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 7 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 8 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 9 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bridged 10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00346] In some embodiments, -S(O)- is -S(=O)-. In some embodiments, -S(O)- is -S ⁺ (-O-)-. In some embodiments, -S(O)- is -S(=O)- and -S ⁺ (-O-)-. [00347] In some embodiments R ¹¹ is p is an integer from 0 to 12; R ^11f is independently hydrogen or R ^11c ; X ¹ is selected from CH ₂ , C=N-OR ^11f , C=NN(R ^11f )(R ^11f ), C(O)N(R ^11f ), N(R ^11f ), O, S, S(O), S(=O)(=NR ^11f ), S(O) ₂ N(R ^11f ), N(R ^11f )S(O)N(R ^11f ), N(R ^11f )S(O) ₂ N(R ^11f ), S(O)N(R ^11f ), OC(O)N(R ^11f ), N(R ^11f )C(O)N(R ^11f ), S(O) ₂ , CH ₂ C=NN(R ^11f )(R ^11f ), C(R ^11f )(R ^11f ), C=N-OR ^11f , C=NN(R ^11f )(R ^11f ), CH ₂ C(R ^11f )(R ^11f ), CH ₂ C(R ^11f )( R ^11f )CH ₂ , C(R ^11f )( R ^11f )C(R ^11f )( R ^11f )C(R ^11f )( R ^11f ), C(R ^11f )( R ^11f )C=N-OR ^11f , C(R ^11f )( R ^11f )C(O)N(R ^11f ), C(R ^11f )( R ^11f )N(R ^11f ), C(R ^11f )( R ^11f )N(H), C(R ^11f )( R ^11f )O, C(R ^11f )( R ^11f )OC(R ^11f )( R ^11f ), C(R ^11f )( R ^11f )S, C(R ^11f )( R ^11f )SC(R ^11f )( R ^11f ), C(R ^11f )( R ^11f )S(O), C(R ^11f )( R ^11f )S(O)C(R ^11f )( R ^11f ), C(R ^11f )( R ^11f )S(O) ₂ C(R ^11f )( R ^11f ), C(R ^11f )( R ^11f )S(=O)(=NR ^11f ), C(R ^11f )( R ^11f )S(O) ₂ N(R ^11f ), C(R ^11f )( R ^11f )N(R ^11f )S(O)N(R ^11f ), C(R ^11f )( R ^11f )N(R ^11f )S(O) ₂ N(R ^11f ), C(R ^11f )( R ^11f )S(O)N(R ^11f ), C(R ^11f )( R ^11f )OC(O)N(R ^11f ), C(R ^11f )( R ^11f )N(R ^11f )C(O)N(R ^11f ), C(R ^11f )(R ^11f )S(O) ₂ , C=NN(R ^11f )( R ^11f )C(R ^11f )( R ^11f ), C(O)N(R ^11f )C(R ^11f )( R ^11f ), S(O) ₂ N(R ^11f )C(R ^11f )( R ^11f ), S(O)N(R ^11f )C(R ^11f )( R ^11f ), and OC(O)N(R ^11f )C(R ^11f )( R ^11f ); X ² is selected from N, C, C(R ⁴ ), CH, N(H), N(R ⁴ ), O, S, S(O), C(R ⁴ )(R ^11f ), CH(R ⁴ ), CH ₂ , S(=O)(=NR ⁴ ), S(O) ₂ ; and X ³ is selected from N, C, and C(R ^11f ). [00348] In embodiments of the formulae above R ¹¹ is [00349] In embodiments of the formulae above R ¹¹ is

and p is an integer from 0 to 12. [00350] In embodiments of the formulae above, R ¹¹ is [00351] In embodiments of the formulae above, R ¹¹ is and p is independently an integer from 0 to 12. [00352] In embodiments of the formulae above, R ¹¹ is [00353] In some embodiments of the formulae above, R ¹¹ is , , , and p is independently an integer from 0 to 12. In embodiments of the formulae above, R ¹¹ is selected from and [00354] In some embodiments of the formulae above, R ¹¹ is

[00355] In some embodiments of the formulae above, R ¹¹ is , , , , , , , In embodiments of the formulae above, R ¹¹ is selected from [00356] In embodiments of the formulae above, R ¹¹ is ¹¹ In embodiments of the formulae above, R is In embodiments of the formulae above, R ¹¹ is In embodiments of the formulae above, R ¹¹ is . In embodiments of the formulae above, R ¹¹ i s . In embodiments of the formulae above, R ¹¹ is In embod ¹¹ iments of the formulae above, R is In embodiments of the formulae above, R ¹¹ is In embodiments of the formulae abo ¹¹ ve, R is In embodiments of the formul ¹¹ ae above, R is [00357] In embodiments of the formulae above, R ¹¹ is a polycyclic C _4-10 cycloalkyl ring system including at least one nitrogen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 3-10 membered heterocycloalkyl including at least one nitrogen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a polycyclic C _7-10 aryl ring system including at least one nitrogen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 5 to 10 membered heteroaryl including at least one nitrogen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00358] In embodiments of the formulae above, R ¹¹ is a polycyclic C _5-10 cycloalkyl ring system including at least one nitrogen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 5-10 membered heterocycloalkyl including at least one nitrogen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00359] In embodiments of the formulae above, R ¹¹ is a 4-10 membered heterocycloalkyl; wherein the 4-10 membered heterocycloalkyl includes at least one nitrogen atom and is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; [00360] In embodiments of the formulae above, R ¹¹ is a polycyclic C _4-10 cycloalkyl ring system including at least one oxygen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 3-10 membered heterocycloalkyl including at least one oxygen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a polycyclic C _7-10 aryl ring system including at least one oxygen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a 5 to 10 membered heteroaryl including at least one oxygen atom and substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00361] In embodiments of the formulae above, R ¹¹ is a C ₃ cycloalkyl substituted with one R ⁴ . In embodiments of the formulae above, R ¹¹ is a C ₃ cycloalkyl substituted with one R ⁴ and substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a C _4-10 cycloalkyl substituted with one R ⁴ . In embodiments of the formulae above, R ¹¹ is a C _4-10 cycloalkyl substituted with one R ⁴ and substituted with one or more R ^11c ; [00362] In embodiments of the formulae above, R ¹¹ is a C ₃ cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00363] In embodiments of the formulae above, R ¹¹ is selected from C _3-12 cycloalkyl, 3-12 membered heterocycloalkyl, C _6-12 aryl, and 5-12 membered heteroaryl; wherein each of C _3-12 cycloalkyl, 3-12 membered heterocycloalkyl, C _6-12 aryl, and 5-12 membered heteroaryl is substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00364] In embodiments of the formulae above, R ¹¹ is C _3-12 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is C _4-10 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is C _{5- 7} cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00365] In embodiments of the formulae above, R ¹¹ is a monocyclic C _3-12 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C _{4- 10} cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic C _5-7 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00366] In embodiments of the formulae above, R ¹¹ is a bicyclic spirocyclic C _5-12 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic spirocyclic C _5-10 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic spirocyclic C _5-7 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00367] In embodiments of the formulae above, R ¹¹ is a bicyclic fused C _4-12 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic fused C _{4- 10} cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic fused C _5-7 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00368] In embodiments of the formulae above, R ¹¹ is 3-12 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is 4-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is 5-7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00369] In embodiments of the formulae above, R ¹¹ is a monocyclic 3-12 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 4-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 5-7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00370] In embodiments of the formulae above, R ¹¹ is a bicyclic spirocyclic 5-12 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic spirocyclic C _5-10 cycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic spirocyclic 5-7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00371] In embodiments of the formulae above, R ¹¹ is a bicyclic fused 4-12 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic fused 4-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic fused 5-7 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00372] In embodiments of the formulae above, R ¹¹ is C _6-12 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is C _6-10 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a phenyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00373] In embodiments of the formulae above, R ¹¹ is a bicyclic fused C _6-12 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic fused C _{6- 10} aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00374] In embodiments of the formulae above, R ¹¹ is 5-12 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is 5-9 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is 5-6 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00375] In embodiments of the formulae above, R ¹¹ is a monocyclic 5-8 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 5- 7 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a monocyclic 5-6 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00376] In embodiments of the formulae above, R ¹¹ is a bicyclic fused 6-12 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic fused 6-10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . In embodiments of the formulae above, R ¹¹ is a bicyclic fused 6-9 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00377] [00378] In embodiments of the formulae above, R ¹¹ i ; W ¹⁴ and W ¹⁵ are independently selected from N(R ^11c ), C(R ^11c )(R ^11c ), N(H), C(H)(R ^11c ), CH ₂ , C(O), S, O, S(O), and S(O) ₂ ; W ¹⁶ and W ¹⁷ are independently selected from C(R ^11c )(R ^11c ), C(H)(R ^11c ), CH ₂ , C(O), S, O, S(O), and S(O) ₂ ; W ¹⁸ is selected from N, CH, and C(R ^11c ); s14 is an integer from 1 to 5; s15 is an integer from 0 to 5; s16 is an integer from 1 to 3; s17 is an integer from 1 to 3. [00379] In embodiments of the formulae above, R ¹¹ is

p independently an integer from 0 to 6. In embodiments of the formulae above, R ¹¹ is selected from

of the formulae above, R ¹¹ is selected from

In embodiments of the formu ¹¹ lae above, R is selected from

and ; and p is an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from

and p is an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from , , , , and p is an integer from 0-8. In embodim ¹¹ ents of the formulae above, R is selected from

and p is an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from

, , , , , and p is an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from , ,

and p is an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from

, , and and p is independently an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from

an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from . In embodiments of the formulae above, R ¹¹ is selected from and p is an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from

, ; and p is an integer from 0-8. In embodiments of the formulae above, R ¹¹ is selected from and p is an integer from 0-3. [00380] It will be understood that when one or more floating substituent(s) is/are shown extending from one ring in a polycyclic ring system (e.g., fused ring system, bridged ring system, or spirocyclic ring system), the one or more floating substituent(s), may be bonded to the ring from which the one or more floating substituents are shown extending or may be bonded to any other ring in the polycyclic ring system and when multiple substituents are represented by the floating substituents, each substituent may be bonded to the same or different rings in the polycyclic ring system, unless indicated otherwise. [00381] In embodiments of the formulae above of the formulae above, R ¹¹ is a single spirocyclic R stereoisomer. In embodiments of the formulae above, R ¹¹ is a single spirocyclic S stereoisomer. In embodiments of the formulae above, R ¹¹ is substituted with one R ^11c substituent wherein the carbon atom attached to the R ^11c substituent is an R isomer. In embodiments of the formulae above, R ¹¹ is substituted with one R ^11c substituent wherein the carbon atom attached to the R ^11c substituent is an S isomer. In embodiments of the formulae above, R ¹¹ is substituted with two optionally different R ^11c substituents wherein the carbon atoms attached to the R ^11c substituents are both R isomers. In embodiments of the formulae above, R ¹¹ is substituted with two optionally different R ^11c substituents wherein the carbon atoms attached to the R ^11c substituents are both S isomers. In embodiments of the formulae above, R ¹¹ is substituted with two optionally different R ^11c substituents wherein the carbon atom attached to one R ^11c substituent is an S isomer and the carbon atom attached to the other R ^11c substituent is an R isomer. [00382] In embodiments of the formulae above of the formulae above, R ¹¹ is a C _3-12 cycloalkyl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . In embodiments of the formulae above of the formulae above, R ¹¹ is a 3-12 membered heterocycloalkyl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . In embodiments of the formulae above of the formulae above, R ¹¹ is a C _6-12 aryl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . In embodiments of the formulae above of the formulae above, R ¹¹ is a 5-12 membered heteroaryl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . In embodiments of the formulae above of the formulae above, R ¹¹ is a C _11-12 cycloalkyl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . In embodiments of the formulae above of the formulae above, R ¹¹ is a 11-12 membered heterocycloalkyl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . In embodiments of the formulae above of the formulae above, R ¹¹ is a C _11-12 aryl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . In embodiments of the formulae above of the formulae above, R ¹¹ is a 11-12 membered heteroaryl substituted with one R ⁴ and is optionally substituted with one or more R ^11c . [00383] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^11a ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00384] In embodiments of the formulae above, R ^11a is independently hydrogen. In embodiments of the formulae above, R ^11a is independently halogen. In embodiments of the formulae above, R ^11a is independently -CN. In embodiments of the formulae above, R ^11a is independently C _1-6 alkyl. In embodiments of the formulae above, R ^11a is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^11a is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^11a is independently C _1-6 haloalkyl. In embodiments of the formulae above, R ^11a is independently C _1-6 alkoxy. In embodiments of the formulae above, R ^11a is independently C _1-6 haloalkoxy. In embodiments of the formulae above, R ^11a is independently C _3-6 cycloalkyl. In embodiments of the formulae above, R ^11a is independently -CH ₂ -C _3-6 cycloalkyl. In embodiments of the formulae above, R ^11a is independently C _{2- 9} heterocycloalkyl. In embodiments of the formulae above, R ^11a is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^11a is independently -OR ¹⁴ . In embodiments of the formulae above, R ^11a is independently -SR ¹⁴ . In embodiments of the formulae above, R ^11a is independently -C(O)OR ¹⁴ . In embodiments of the formulae above, R ^11a is independently -C(O)N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11a is independently -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11a is independently - OC(O)N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11a is independently -C(O)R ^14a . In embodiments of the formulae above, R ^11a is independently -S(O) ₂ R ¹⁴ . In embodiments of the formulae above, R ^11a is independently - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11a is independently -OCH ₂ C(O)OR ¹⁴ . In embodiments of the formulae above, R ^11a is independently -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently -N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11a is independently - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11a is independently -N(R ¹⁴ )C(O)OR ¹⁴ . In embodiments of the formulae above, R ^11a is independently -N(R ¹⁴ )C(O)R ^14a . In embodiments of the formulae above, R ^11a is independently -N(R ¹⁴ )S(O) ₂ R ¹⁴ . [00385] In embodiments of the formulae above, R ^11a is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , - C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , - N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently C _1-6 haloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , - N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently C _1-6 alkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently C _1-6 haloalkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently C _3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently -CH ₂ -C _3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently C ₂ - ₉ heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11a is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . [00386] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^11b ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00387] In embodiments of the formulae above, R ^11b is independently hydrogen. In embodiments of the formulae above, R ^11b is independently -CN. In embodiments of the formulae above, R ^11b is independently C _1-6 alkyl. In embodiments of the formulae above, R ^11b is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^11b is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^11b is independently C _1-6 haloalkyl. In embodiments of the formulae above, R ^11b is independently C _1-6 alkoxy. In embodiments of the formulae above, R ^11b is independently C _1-6 haloalkoxy. In embodiments of the formulae above, R ^11b is independently C _3-6 cycloalkyl. In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _3-6 cycloalkyl. In embodiments of the formulae above, R ^11b is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^11b is independently - CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ^11b is independently -OR ¹⁴ . In embodiments of the formulae above, R ^11b is independently -SR ¹⁴ . In embodiments of the formulae above, R ^11b is independently - C(O)OR ¹⁴ . In embodiments of the formulae above, R ^11b is independently -C(O)N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11b is independently -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11b is independently -OC(O)N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11b is independently -C(O)R ^14a . In embodiments of the formulae above, R ^11b is independently -S(O) ₂ R ¹⁴ . In embodiments of the formulae above, R ^11b is independently -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ) . In embodiments of the formulae above, R ^11b is independently - OCH ₂ C(O)OR ¹⁴ . In embodiments of the formulae above, R ^11b is independently -OC(O)R ^14a . [00388] In embodiments of the formulae above, R ^11b is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , - C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , - N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently C _1-6 haloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , - N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently C _1-6 alkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently C _1-6 haloalkoxy optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently C _3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , - S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), - C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), - N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , -N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a . [00389] In embodiments of the formulae above, R ^11b is independently C _1-6 alkyl. In embodiments of the formulae above, R ^11b is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^11b is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^11b is independently C _1-6 haloalkyl, C _3-12 cycloalkyl. In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _3-12 cycloalkyl. In embodiments of the formulae above, R ^11b is independently C _1-11 heterocycloalkyl. In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _1- 11heterocycloalkyl. In embodiments of the formulae above, R ^11b is independently C _6-12 aryl. In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _6-12 aryl. In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _1-11 heteroaryl. In embodiments of the formulae above, R ^11b is independently C _1-11 heteroaryl. [00390] In embodiments of the formulae above, R ^11b is independently C _1-6 alkyl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently C _2-6 alkenyl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently C _2-6 alkynyl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently C _1-6 haloalkyl, C _3-12 cycloalkyl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _3-12 cycloalkyl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently C _1-11 heterocycloalkyl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _1-11 heterocycloalkyl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently C _6-12 aryl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _6-12 aryl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently -CH ₂ -C _{1- 11} heteroaryl substituted with one or more R ^20g . In embodiments of the formulae above, R ^11b is independently C _{1- 11} heteroaryl substituted with one or more R ^20g . [00391] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^11c ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00392] In embodiments of the formulae above, two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are joined to form a C _3-12 cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are joined to form a C _1-11 heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are joined to form a C _6-12 aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are joined to form a C _1-11 heteroaryl, optionally substituted with one, two, or three R ^20g optionally substituted with one, two, or three R ^20g In embodiments of the formulae above, one R ^11c and one R ⁴ that are bonded to the same atom are joined to form [00393] In embodiments of the formulae above, R ^11c is independently selected from hydrogen, halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, -OR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), and -C(O)R ¹⁵ , wherein C _{1- 6} alkyl, C _2-6 alkenyl, and C _2-6 alkynyl, are optionally substituted with one, two, or three R ^20a . In embodiments of the formulae above, R ^11c is independently hydrogen. In embodiments of the formulae above, R ^11c is independently halogen. In embodiments of the formulae above, R ^11c is independently oxo. In embodiments of the formulae above, R ^11c is independently -CN. In embodiments of the formulae above, R ^11c is independently C _1-6 alkyl. In embodiments of the formulae above, R ^11c is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^11c is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^11c is independently -OR ¹² . In select embodiments of the subject compound, R ^11c is independently -N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^11c is independently -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -C(O)R ¹⁵ . In select embodiments of the subject compound, R ^11c is independently -NH ₂ . In embodiments of the formulae above, R ^11c is independently -C(O)OH. In embodiments of the formulae above, R ^11c is independently -OC(O)NH ₂ . In embodiments of the formulae above, R ^11c is independently -C(O)CH ₃ . [00394] In embodiments of the formulae above, R ^11c is independently halogen. In embodiments of the formulae above. In embodiments of the formulae above, R ^11c is independently oxo. In embodiments of the formulae above, R ^11c is independently -CN. In embodiments of the formulae above, R ^11c is independently C _1-6 alkyl. In embodiments of the formulae above, R ^11c is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^11c is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^11c is independently C _1-6 haloalkyl. In embodiments of the formulae above, R ^11c is independently C _3-12 cycloalkyl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _3-12 cycloalkyl. In embodiments of the formulae above, R ^11c is independently C _1- 11heterocycloalkyl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heterocycloalkyl. In embodiments of the formulae above, R ^11c is independently C _6-12 aryl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _6-12 aryl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heteroaryl. In embodiments of the formulae above, R ^11c is independently C _1-11 heteroaryl. In embodiments of the formulae above, R ^11c is independently -OR ¹² . In embodiments of the formulae above, R ^11c is independently -SR ¹² . In embodiments of the formulae above, R ^11c is independently -N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^11c is independently -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -C(O)R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -S(O)R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -C(O)C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^11c is independently - S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -S(O) ₂ N(R ¹² )(R ¹³ )-. In embodiments of the formulae above, R ^11c is independently S(=O)(=NH)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently - CH ₂ C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^11c is independently and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). [00395] In embodiments of the formulae above, R ^11c is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _2-6 alkynyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-6 haloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _3- 12cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _3-12 cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-11 heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _6-12 aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _{6- 12} aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heteroaryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-11 heteroaryl optionally substituted with one, two, or three R ^20g . [00396] In embodiments of the formulae above, two R ^11c substituents are joined to form a C _3-12 cycloalkyl. In embodiments of the formulae above, two R ^11c substituents are joined to form a C _1-11 heterocycloalkyl. In embodiments of the formulae above, two R ^11c substituents are joined to form a C _6-12 aryl. In embodiments of the formulae above, two R ^11c substituents are joined to form a C _1-11 heteroaryl. [00397] In embodiments of the formulae above, two R ^11c substituents are joined to form a C _3-12 cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c substituents are joined to form a C _1-11 heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c substituents are joined to form a C _6-12 aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c substituents are joined to form a C _1-11 heteroaryl optionally substituted with one, two, or three R ^20g . [00398] In embodiments of the formulae above, each R ^11c is independently selected from halogen, oxo, -CN, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). [00399] In embodiments of the formulae above, each R ^11c is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _{6- 12} aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{1- 6} haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, - CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, each R ^11c is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{1- 6} haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, and C _1-11 heterocycloalkyl. [00400] In embodiments of the formulae above, R ^11c is independently C _1-6 alkyl. In embodiments of the formulae above, R ^11c is independently C _2-6 alkenyl. In embodiments of the formulae above, R ^11c is independently C _2-6 alkynyl. In embodiments of the formulae above, R ^11c is independently C _1-6 haloalkyl. In embodiments of the formulae above, R ^11c is independently C _3-12 cycloalkyl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _{3- 12} cycloalkyl. In embodiments of the formulae above, R ^11c is independently C _1-11 heterocycloalkyl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heterocycloalkyl. In embodiments of the formulae above, R ^11c is independently C _6-12 aryl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _6-12 aryl. In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heteroaryl. In embodiments of the formulae above, R ^11c is independently C _1-11 heteroaryl. [00401] In embodiments of the formulae above, R ^11c is independently C _1-6 alkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _2-6 alkenyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _2-6 alkynyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-6 haloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _{3- 12} cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _3-12 cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-11 heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _6-12 aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C ₆ - ₁₂ aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -CH ₂ -C _1-11 heteroaryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-11 heteroaryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-4 alkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1-3 alkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently methyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently ethyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently propyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently isopropyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently cyclopropyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently cyclobutyl optionally substituted with one, two, or three R ^20g . [00402] In embodiments of the formulae above, R ^11c is independently halogen. In embodiments of the formulae above, R ^11c is independently oxo. In embodiments of the formulae above, R ^11c is independently -CN. In embodiments of the formulae above, R ^11c is independently -OR ¹² . In embodiments of the formulae above, R ^11c is independently -SR ¹² . In embodiments of the formulae above, R ^11c is independently -N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, R ^11c is independently -C(O)OR ¹² . In embodiments of the formulae above, R ^11c is independently -OC(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )C(O)OR ¹⁵ . In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -C(O)R ¹² . In embodiments of the formulae above, R ^11c is independently -S(O)R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -OC(O)R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -C(O)C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -N(R ¹⁴ )C(O)R ¹² . In embodiments of the formulae above, R ^11c is independently - S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently S(=O)(=NH)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -CH ₂ C(O)N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently - CH ₂ N(R ¹⁴ )C(O)R ¹² . In embodiments of the formulae above, R ^11c is independently -CH ₂ S(O) ₂ R ¹⁵ . In embodiments of the formulae above, R ^11c is independently -CH ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently -CH ₂ CN. In embodiments of the formulae above, R ^11c is independently -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ). In embodiments of the formulae above, R ^11c is independently F. In embodiments of the formulae above, R ^11c is independently Cl. In embodiments of the formulae above, R ^11c is independently Br. In embodiments of the formulae above, R ^11c is independently I. In embodiments of the formulae above, R ^11c is independently -OH. In embodiments of the formulae above, R ^11c is independently -SH. In embodiments of the formulae above, R ^11c is independently -NH ₂ . [00403] In embodiments of the formulae above, two R ^11c are optionally joined to form a C _3-12 cycloalkyl. In embodiments of the formulae above, two R ^11c are optionally joined to form a C _2-11 heterocycloalkyl. In embodiments of the formulae above, two R ^11c are optionally joined to form a C _6-12 aryl. In embodiments of the formulae above, two R ^11c are optionally joined to form a C _1-11 heteroaryl. [00404] In embodiments of the formulae above, two R ^11c are optionally joined to form a C _3-12 cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c are optionally joined to form a C _2-11 heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c are optionally joined to form a C _6-12 aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, two R ^11c are optionally joined to form a C _1-11 heteroaryl optionally substituted with one, two, or three R ^20g . [00405] In embodiments of the formulae above, R ^11c is independently C _3-12 cycloalkyl. In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _3-12 cycloalkyl). In embodiments of the formulae above, R ^11c is independently C _2-11 heterocycloalkyl. In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _2- 11heterocycloalkyl). In embodiments of the formulae above, R ^11c is independently C _6-12 aryl. In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _6-12 aryl). In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _1-11 heteroaryl). In embodiments of the formulae above, R ^11c is independently C _{1- 11} heteroaryl. [00406] In embodiments of the formulae above, R ^11c is independently C _3-12 cycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _{2- 11} heterocycloalkyl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _6-12 aryl optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _0-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently C _1- 11heteroaryl optionally substituted with one, two, or three R ^20g . [00407] In embodiments of the formulae above, R ^11c is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _1-6 alkyl- (C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-6 alkyl- (C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-3 alkyl- (C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20g . In embodiments of the formulae above, R ^11c is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20g . [00408] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ¹² ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00409] In embodiments of the formulae above, R ¹² is hydrogen. In embodiments of the formulae above, R ¹² is C _{1- 6} alkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is methylene optionally substituted with one or two R ^20d . In embodiments of the formulae above, R ¹² is methylene. In embodiments of the formulae above, R ¹² is ethylene optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is ethylene. In embodiments of the formulae above, R ¹² is propylene optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is propylene. In embodiments of the formulae above, R ¹² is -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -(monocyclic C _2-8 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -(monocyclic C _3-5 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -(spirocyclic C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -(spirocyclic C _3-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -(fused C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -(spirocyclic C _6-8 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH(CH ₃ )-C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH(CH ₃ )-(monocyclic C _{2- 8} heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH(CH ₃ )-(monocyclic C _3-5 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH(CH ₃ )-(spirocyclic C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH(CH ₃ )-(spirocyclic C _3-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH(CH ₃ )-(fused C _{2- 11} heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH(CH ₃ )-(spirocyclic C _6-8 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . [00410] In embodiments of the formulae above, R ¹² is C _1-6 alkyl. In embodiments of the formulae above, R ¹² is C ₂ - ₆ alkenyl. In embodiments of the formulae above, R ¹² is C _2-6 alkynyl. In embodiments of the formulae above, R ¹² is C _3-10 cycloalkyl. In embodiments of the formulae above, R ¹² is -CH ₂ -C _3-10 cycloalkyl. In embodiments of the formulae above, R ¹² is C _2-9 heterocycloalkyl. In embodiments of the formulae above, R ¹² is -CH ₂ -C ₂ - ₉ heterocycloalkyl. In embodiments of the formulae above, R ¹² is C _6-10 aryl. In embodiments of the formulae above, R ¹² is -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, R ¹² is -CH ₂ -C _1-9 heteroaryl. In embodiments of the formulae above, R ¹² is C _1-9 heteroaryl. [00411] In embodiments of the formulae above, R ¹² is C _1-6 alkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is C _2-6 alkenyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is C _2-6 alkynyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is C _6-10 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -C _6-10 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is C _1-9 heteroaryl optionally substituted with one, two, or three R ^20d . [00412] In embodiments of the formulae above, R ¹² is independently C _3-12 cycloalkyl. In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _3-12 cycloalkyl). In embodiments of the formulae above, R ¹² is independently C _2-11 heterocycloalkyl. In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _{2- 11} heterocycloalkyl). In embodiments of the formulae above, R ¹² is independently C _6-12 aryl. In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _6-12 aryl). In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _1-11 heteroaryl). In embodiments of the formulae above, R ¹² is independently C _{1- 11} heteroaryl. [00413] In embodiments of the formulae above, R ¹² is independently C _3-12 cycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently C ₂ - ₁₁ heterocycloalkyl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently C _6-12 aryl optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _0-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently C _{1- 11} heteroaryl optionally substituted with one, two, or three R ^20d . [00414] In embodiments of the formulae above, R ¹² is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _1-6 alkyl- (C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-6 alkyl- (C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-3 alkyl- (C _2-11 heterocycloalkyl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, R ¹² is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three R ^20d . [00415] [00416] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ¹⁷ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00417] In embodiments of the formulae above, R ¹⁷ is selected from: , Q ³ is N or C(R ^1d ); Q ⁴ is O or S; X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , - SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , - N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , - S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , - CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . [00418] In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is [00419] In embodiments of the formulae above, R ¹⁷ is: Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . [00420] In embodiments of the formulae above, R ¹⁷ i Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . [00421] In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is n embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the fo ¹⁷ rmulae above, R is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . [00422] In embodiments of the formulae above, R ¹⁷ is selected from: , ,

[00423] In embodiments of the formulae above, R ¹⁷ is selected from: , , and [00424] In embodiments of the formulae above, R ¹⁷ is selected from , and In embodiments of the formulae above, R ¹⁷ is selected from and [00425] In embodiments of the formulae above, R ¹⁷ is wherein X ⁹ , X ¹⁰ , X ¹¹ , Q ³ , Q ⁴ , and R ^1h are as described herein. In embodiments of the formulae above, R ¹⁷ is wherein X ⁹ , X ¹⁰ , X ¹¹ , Q ³ , Q ⁴ , and R ^1h are as described herein. In embodiments of the formulae above, R ¹⁷ is wherein X ⁹ , X ¹⁰ , X ¹¹ , Q ³ , Q ⁴ , R ^1a , and R ^1h are as described herein. In embodiments of the formulae above, R ¹⁷ is wherein X ⁹ , X ¹⁰ , X ¹¹ , ^{3 4 1a 1h} Q, Q, R , and R are as described herein. [00426] In embodiments of the formulae above, R ¹⁷ is ^{9 10 11 12 3 4} wherein X, X , X , X , Q, Q, and R ^1h are as described herein. In embodiments of the formulae above, R ¹⁷ is wherein X ⁹ , X ¹⁰ , X ¹¹ , X ¹² , Q ³ , Q ⁴ , and R ^1h are as described herein. [00427] In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is . In embodiments of the formulae above, R ¹⁷ is In embodiments of the formulae above, R ¹⁷ is [00428] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of Q ³ , Q ⁴ , X ⁹ , X ¹⁰ , X ¹¹ , and X ¹² ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00429] In embodiments of the formulae above, Q ³ is N. In embodiments of the formulae above, Q ³ is C(R ^1d ). In embodiments of the formulae above, Q ⁴ is O. In embodiments of the formulae above, Q ⁴ is S. In embodiments of the formulae above, Q ⁴ is N(R ^1c ). In embodiments of the formulae above, X ⁹ is independently C(O). In embodiments of the formulae above, X ⁹ is independently C(R ^1a ). In embodiments of the formulae above, X ⁹ is independently C(R ^1a )(R ^1b ). In embodiments of the formulae above, X ¹⁰ is independently C(O). In embodiments of the formulae above, X ¹⁰ is independently C(R ^1a ). In embodiments of the formulae above, X ¹⁰ is independently C(R ^1a )(R ^1b ). In embodiments of the formulae above, X ¹¹ is independently C(O). In embodiments of the formulae above, X ¹¹ is independently C(R ^1a ). In embodiments of the formulae above, X ¹¹ is independently C(R ^1a )(R ^1b ). In embodiments of the formulae above, X ¹² is C. In embodiments of the formulae above, X ¹² is C(R ^1a ). [00430] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00431] In embodiments of the formulae above, R ^20a is independently selected from halogen, -CN, C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently selected from halogen, -CN, C _1-6 alkyl, -OR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)R ²⁵ , and - OC(O)R ²⁵ , wherein C _1-6 alkyl is optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00432] In embodiments of the formulae above, each R ^20a is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00433] In embodiments of the formulae above, each R ^20a is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently halogen. In embodiments of the formulae above, each R ^20a is independently oxo. In embodiments of the formulae above, each R ^20a is independently -CN. In embodiments of the formulae above, each R ^20a is independently -OR ²¹ . In embodiments of the formulae above, each R ^20a is independently -SR ²¹ . In embodiments of the formulae above, each R ^20a is independently -N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20a is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, each R ^20a is independently -C(O)OR ²² . In embodiments of the formulae above, each R ^20a is independently -C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20a is independently -C(O)C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20a is independently -OC(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20a is independently - N(R ²⁴ )C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20a is independently -N(R ²⁴ )C(O)OR ²⁵ . In embodiments of the formulae above, each R ^20a is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, each R ^20a is independently -N(R ²⁴ )S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -C(O)R ²¹ . In embodiments of the formulae above, each R ^20a is independently -S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -S(O) ₂ N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20a is independently -OCH ₂ C(O)OR ²² . In embodiments of the formulae above, each R ^20a is independently -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently F. In embodiments of the formulae above, each R ^20a is independently Cl. In embodiments of the formulae above, each R ^20a is independently Br. In embodiments of the formulae above, each R ^20a is independently I. In embodiments of the formulae above, each R ^20a is independently -OH. In embodiments of the formulae above, each R ^20a is independently -SH. In embodiments of the formulae above, each R ^20a is independently -NH ₂ . In embodiments of the formulae above, each R ^20a is independently =C(H) ₂ . In embodiments of the formulae above, each R ^20a is independently - C(O)OH. In embodiments of the formulae above, each R ^20a is independently -C(O)NH ₂ . In embodiments of the formulae above, each R ^20a is independently -C(O)C(O)NH ₂ . In embodiments of the formulae above, each R ^20a is independently -OC(O)NH ₂ . In embodiments of the formulae above, each R ^20a is independently -NHC(O)NH ₂ . In embodiments of the formulae above, each R ^20a is independently -NHC(O)OH. In embodiments of the formulae above, each R ^20a is independently -NHC(O)H. In embodiments of the formulae above, each R ^20a is independently - NHS(O) ₂ H. In embodiments of the formulae above, each R ^20a is independently -C(O)H. In embodiments of the formulae above, each R ^20a is independently -S(O) ₂ H. In embodiments of the formulae above, each R ^20a is independently -S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ^20a is independently -OCH ₂ C(O)OH. In embodiments of the formulae above, each R ^20a is independently -OC(O)H. [00434] In embodiments of the formulae above, each R ^20a is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C ₆ - ₁₀ aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _{2- 7} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C1-5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _{1- 5} heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00435] In embodiments of the formulae above, each R ^20a is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C ₂ - ₉ heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _{2- 7} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20a is independently C _1- 5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00436] In embodiments of the formulae above, each R ^20a is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C ₆ - ₁₀ aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20a is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20a is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20a is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20a is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20a is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20a is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _1- 9heteroaryl. In embodiments of the formulae above, each R ^20a is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20a is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20a is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20a is independently methyl. In embodiments of the formulae above, each R ^20a is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20a is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20a is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20a is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C ₂ - ₇ heterocycloalkyl. In embodiments of the formulae above, each R ^20a is independently phenyl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20a is independently -CH ₂ -C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20a is independently C _1- 5heteroaryl. [00437] In embodiments of the formulae above, R ^20a is independently C _3-12 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently C _{2- 11} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently C _6-12 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently C _1-11 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00438] In embodiments of the formulae above, R ^20a is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _1-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-6 alkyl-(C _{3- 12} cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-6 alkyl-(C _{1- 11} heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-3 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20a is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, R ^20a is independently =NR ²¹ . In embodiments of the formulae above, R ^20a is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, R ^20a is independently -C(O)R ²¹ . [00439] In embodiments of the formulae above, each R ^20b is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00440] In embodiments of the formulae above, each R ^20b is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00441] In embodiments of the formulae above, each R ^20b is independently halogen. In embodiments of the formulae above, each R ^20b is independently oxo. In embodiments of the formulae above, each R ^20b is independently -CN. In embodiments of the formulae above, each R ^20b is independently -OR ²¹ . In embodiments of the formulae above, each R ^20b is independently -SR ²¹ . In embodiments of the formulae above, each R ^20b is independently - N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20b is independently F. In embodiments of the formulae above, each R ^20b is independently Cl. In embodiments of the formulae above, each R ^20b is independently Br. In embodiments of the formulae above, each R ^20b is independently I. In embodiments of the formulae above, each R ^20b is independently -OH. In embodiments of the formulae above, each R ^20b is independently -SH. In embodiments of the formulae above, each R ^20b is independently -NH ₂ . In embodiments of the formulae above, each R ^20b is independently selected from =C(H) ₂ , -C(O)OH, -C(O)NH ₂ , -C(O)C(O)NH ₂ , -OC(O)NH ₂ , -NHC(O)NH ₂ , - NHC(O)OH, -NHC(O)H, -NHS(O) ₂ H, -C(O)H, -S(O) ₂ H, -S(O) ₂ NH ₂ , -OCH ₂ C(O)OH, and -OC(O)H. [00442] In embodiments of the formulae above, each R ^20b is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20b is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, -CH ₂ - C _3-7 cycloalkyl, C ₂ - ₇ heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl, wherein C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, -CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _{2- 7} heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20b is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00443] In embodiments of the formulae above, each R ^20b is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C ₆ - ₁₀ aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20b is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20b is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20b is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20b is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20b is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20b is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -C _1- 9heteroaryl. In embodiments of the formulae above, each R ^20b is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20b is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20b is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20b is independently methyl. In embodiments of the formulae above, each R ^20b is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20b is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20b is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20b is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -C ₂ - ₇ heterocycloalkyl. In embodiments of the formulae above, each R ^20b is independently phenyl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20b is independently -CH ₂ -C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20b is independently C _1- 5heteroaryl. [00444] In embodiments of the formulae above, each R ^20c is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00445] In embodiments of the formulae above, each R ^20c is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00446] In embodiments of the formulae above, each R ^20c is independently halogen. In embodiments of the formulae above, each R ^20c is independently oxo. In embodiments of the formulae above, each R ^20c is independently -CN. In embodiments of the formulae above, each R ^20c is independently -OR ²¹ . In embodiments of the formulae above, each R ^20c is independently -SR ²¹ . In embodiments of the formulae above, each R ^20c is independently - N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20c is independently F. In embodiments of the formulae above, each R ^20c is independently Cl. In embodiments of the formulae above, each R ^20c is independently Br. In embodiments of the formulae above, each R ^20c is independently I. In embodiments of the formulae above, each R ^20c is independently -OH. In embodiments of the formulae above, each R ^20c is independently -SH. In embodiments of the formulae above, each R ^20c is independently -NH ₂ . In embodiments of the formulae above, each R ^20c is independently selected from =C(H) ₂ , -C(O)OH, -C(O)NH ₂ , -C(O)C(O)NH ₂ , -OC(O)NH ₂ , -NHC(O)NH ₂ , - NHC(O)OH, -NHC(O)H, -NHS(O) ₂ H, -C(O)H, -S(O) ₂ H, -S(O) ₂ NH ₂ , -OCH ₂ C(O)OH, and -OC(O)H. [00447] In embodiments of the formulae above, each R ^20c is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C ₆ - ₁₀ aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20c is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, -CH ₂ -C _3-7 cycloalkyl, C _{2- 7} heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl, wherein C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, -CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C ₂ - ₇ heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20c is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00448] In embodiments of the formulae above, each R ^20c is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20c is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20c is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20c is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20c is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20c is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20c is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -C _1- 9heteroaryl. In embodiments of the formulae above, each R ^20c is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20c is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20c is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20c is independently methyl. In embodiments of the formulae above, each R ^20c is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20c is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20c is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20c is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -C _2- 7heterocycloalkyl. In embodiments of the formulae above, each R ^20c is independently phenyl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20c is independently -CH ₂ -C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20c is independently C _{1- 5} heteroaryl. [00449] In embodiments of the formulae above, R ^20d is independently selected from halogen, -CN, C _1-6 alkyl, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently selected from halogen, -CN, C _1-6 alkyl, -OR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)R ²⁵ , and - OC(O)R ²⁵ , wherein C _1-6 alkyl is optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00450] In embodiments of the formulae above, each R ^20d is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00451] In embodiments of the formulae above, each R ^20d is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently halogen. In embodiments of the formulae above, each R ^20d is independently oxo. In embodiments of the formulae above, each R ^20d is independently -CN. In embodiments of the formulae above, each R ^20d is independently -OR ²¹ . In embodiments of the formulae above, each R ^20d is independently -SR ²¹ . In embodiments of the formulae above, each R ^20d is independently -N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20d is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, each R ^20d is independently -C(O)OR ²² . In embodiments of the formulae above, each R ^20d is independently -C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20d is independently -C(O)C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20d is independently -OC(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20d is independently - N(R ²⁴ )C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20d is independently -N(R ²⁴ )C(O)OR ²⁵ . In embodiments of the formulae above, each R ^20d is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, each R ^20d is independently -N(R ²⁴ )S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -C(O)R ²¹ . In embodiments of the formulae above, each R ^20d is independently -S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -S(O) ₂ N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20d is independently -OCH ₂ C(O)OR ²² . In embodiments of the formulae above, each R ^20d is independently -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently F. In embodiments of the formulae above, each R ^20d is independently Cl. In embodiments of the formulae above, each R ^20d is independently Br. In embodiments of the formulae above, each R ^20d is independently I. In embodiments of the formulae above, each R ^20d is independently -OH. In embodiments of the formulae above, each R ^20d is independently -SH. In embodiments of the formulae above, each R ^20d is independently -NH ₂ . In embodiments of the formulae above, each R ^20d is independently =C(H) ₂ . In embodiments of the formulae above, each R ^20d is independently - C(O)OH. In embodiments of the formulae above, each R ^20d is independently -C(O)NH ₂ . In embodiments of the formulae above, each R ^20d is independently -C(O)C(O)NH ₂ . In embodiments of the formulae above, each R ^20d is independently -OC(O)NH ₂ . In embodiments of the formulae above, each R ^20d is independently -NHC(O)NH ₂ . In embodiments of the formulae above, each R ^20d is independently -NHC(O)OH. In embodiments of the formulae above, each R ^20d is independently -NHC(O)H. In embodiments of the formulae above, each R ^20d is independently - NHS(O) ₂ H. In embodiments of the formulae above, each R ^20d is independently -C(O)H. In embodiments of the formulae above, each R ^20d is independently -S(O) ₂ H. In embodiments of the formulae above, each R ^20d is independently -S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ^20d is independently -OCH ₂ C(O)OH. In embodiments of the formulae above, each R ^20d is independently -OC(O)H. [00452] In embodiments of the formulae above, each R ^20d is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C ₂ - ₉ heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C ₆ - ₁₀ aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _{2- 7} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _{1- 5} heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00453] In embodiments of the formulae above, each R ^20d is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _3- 7cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _3- 7cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _2- 7heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20d is independently C _1- 5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00454] In embodiments of the formulae above, each R ^20d is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20d is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20d is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20d is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20d is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20d is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20d is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _{1- 9} heteroaryl. In embodiments of the formulae above, each R ^20d is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20d is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C1-5heteroaryl, and C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20d is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20d is independently methyl. In embodiments of the formulae above, each R ^20d is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20d is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20d is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20d is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C _{2- 7} heterocycloalkyl. In embodiments of the formulae above, each R ^20d is independently phenyl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20d is independently -CH ₂ -C1-5heteroaryl. In embodiments of the formulae above, each R ^20d is independently C _1- 5heteroaryl. [00455] In embodiments of the formulae above, R ^20d is independently C _3-12 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently C _{2- 11} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently C _6-12 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently C _1-11 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00456] In embodiments of the formulae above, R ^20d is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _1-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-6 alkyl-(C _3- 12cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-6 alkyl-(C _1- 11heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-3 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20d is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, R ^20d is independently =NR ²¹ . In embodiments of the formulae above, R ^20d is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, R ^20d is independently -C(O)R ²¹ . [00457] In embodiments of the formulae above, each R ^20e is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00458] In embodiments of the formulae above, each R ^20e is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00459] In embodiments of the formulae above, each R ^20e is independently halogen. In embodiments of the formulae above, each R ^20e is independently oxo. In embodiments of the formulae above, each R ^20e is independently -CN. In embodiments of the formulae above, each R ^20e is independently -OR ²¹ . In embodiments of the formulae above, each R ^20e is independently -SR ²¹ . In embodiments of the formulae above, each R ^20e is independently - N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20e is independently F. In embodiments of the formulae above, each R ^20e is independently Cl. In embodiments of the formulae above, each R ^20e is independently Br. In embodiments of the formulae above, each R ^20e is independently I. In embodiments of the formulae above, each R ^20e is independently -OH. In embodiments of the formulae above, each R ^20e is independently -SH. In embodiments of the formulae above, each R ^20e is independently -NH ₂ . In embodiments of the formulae above, each R ^20e is independently selected from =C(H) ₂ , -C(O)OH, -C(O)NH ₂ , -C(O)C(O)NH ₂ , -OC(O)NH ₂ , -NHC(O)NH ₂ , - NHC(O)OH, -NHC(O)H, -NHS(O) ₂ H, -C(O)H, -S(O) ₂ H, -S(O) ₂ NH ₂ , -OCH ₂ C(O)OH, and -OC(O)H. [00460] In embodiments of the formulae above, each R ^20e is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20e is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, -CH ₂ -C _3-7 cycloalkyl, C ₂ - ₇ heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl, wherein C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, -CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _{2- 7} heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20e is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00461] In embodiments of the formulae above, each R ^20e is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20e is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20e is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20e is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20e is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20e is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20e is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -C _{1- 9} heteroaryl. In embodiments of the formulae above, each R ^20e is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20e is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C1-5heteroaryl. In embodiments of the formulae above, each R ^20e is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20e is independently methyl. In embodiments of the formulae above, each R ^20e is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20e is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20e is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20e is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -C ₂ - ₇ heterocycloalkyl. In embodiments of the formulae above, each R ^20e is independently phenyl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20e is independently -CH ₂ -C1-5heteroaryl. In embodiments of the formulae above, each R ^20e is independently C _1- 5heteroaryl. [00462] In embodiments of the formulae above, R ^20f is independently selected from halogen, -CN, C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently selected from halogen, -CN, C _1-6 alkyl, -OR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)R ²⁵ , and -OC(O)R ²⁵ , wherein C _1-6 alkyl is optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00463] In embodiments of the formulae above, each R ^20f is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00464] In embodiments of the formulae above, each R ^20f is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently halogen. In embodiments of the formulae above, each R ^20f is independently oxo. In embodiments of the formulae above, each R ^20f is independently -CN. In embodiments of the formulae above, each R ^20f is independently -OR ²¹ . In embodiments of the formulae above, each R ^20f is independently -SR ²¹ . In embodiments of the formulae above, each R ^20f is independently -N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20f is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, each R ^20f is independently -C(O)OR ²² . In embodiments of the formulae above, each R ^20f is independently -C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20f is independently -C(O)C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20f is independently -OC(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20f is independently - N(R ²⁴ )C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20f is independently -N(R ²⁴ )C(O)OR ²⁵ . In embodiments of the formulae above, each R ^20f is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, each R ^20f is independently -N(R ²⁴ )S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -C(O)R ²¹ . In embodiments of the formulae above, each R ^20f is independently -S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -S(O) ₂ N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20f is independently -OCH ₂ C(O)OR ²² . In embodiments of the formulae above, each R ^20f is independently -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently F. In embodiments of the formulae above, each R ^20f is independently Cl. In embodiments of the formulae above, each R ^20f is independently Br. In embodiments of the formulae above, each R ^20f is independently I. In embodiments of the formulae above, each R ^20f is independently -OH. In embodiments of the formulae above, each R ^20f is independently -SH. In embodiments of the formulae above, each R ^20f is independently -NH ₂ . In embodiments of the formulae above, each R ^20f is independently =C(H) ₂ . In embodiments of the formulae above, each R ^20f is independently - C(O)OH. In embodiments of the formulae above, each R ^20f is independently -C(O)NH ₂ . In embodiments of the formulae above, each R ^20f is independently -C(O)C(O)NH ₂ . In embodiments of the formulae above, each R ^20f is independently -OC(O)NH ₂ . In embodiments of the formulae above, each R ^20f is independently -NHC(O)NH ₂ . In embodiments of the formulae above, each R ^20f is independently -NHC(O)OH. In embodiments of the formulae above, each R ^20f is independently -NHC(O)H. In embodiments of the formulae above, each R ^20f is independently - NHS(O) ₂ H. In embodiments of the formulae above, each R ^20f is independently -C(O)H. In embodiments of the formulae above, each R ^20f is independently -S(O) ₂ H. In embodiments of the formulae above, each R ^20f is independently -S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ^20f is independently -OCH ₂ C(O)OH. In embodiments of the formulae above, each R ^20f is independently -OC(O)H. [00465] In embodiments of the formulae above, each R ^20f is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _3- 7cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _2- 7heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C1-5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C1-5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00466] In embodiments of the formulae above, each R ^20f is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C ₆ - ₁₀ aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C ₂ - ₉ heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C ₆ - ₁₀ aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C ₂ - ₇ heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20f is independently C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00467] In embodiments of the formulae above, each R ^20f is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20f is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20f is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20f is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20f is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20f is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20f is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _1- 9heteroaryl. In embodiments of the formulae above, each R ^20f is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20f is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20f is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20f is independently methyl. In embodiments of the formulae above, each R ^20f is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20f is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20f is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20f is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _2- 7heterocycloalkyl. In embodiments of the formulae above, each R ^20f is independently phenyl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20f is independently -CH ₂ -C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20f is independently C _{1- 5} heteroaryl. [00468] In embodiments of the formulae above, R ^20f is independently C _3-12 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently C ₂ - 11heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently C _6-12 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently C _1-11 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00469] In embodiments of the formulae above, R ^20f is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _1-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-6 alkyl-(C _{3- 12} cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-6 alkyl-(C _{1- 11} heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-3 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20f is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, R ^20f is independently =NR ²¹ . In embodiments of the formulae above, R ^20f is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, R ^20f is independently -C(O)R ²¹ . [00470] In embodiments of the formulae above, each R ^20g is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00471] In embodiments of the formulae above, each R ^20g is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently halogen. In embodiments of the formulae above, each R ^20g is independently oxo. In embodiments of the formulae above, each R ^20g is independently -CN. In embodiments of the formulae above, each R ^20g is independently -OR ²¹ . In embodiments of the formulae above, each R ^20g is independently -SR ²¹ . In embodiments of the formulae above, each R ^20g is independently -N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20g is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, each R ^20g is independently -C(O)OR ²² . In embodiments of the formulae above, each R ^20g is independently -C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20g is independently -C(O)C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20g is independently -OC(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20g is independently - N(R ²⁴ )C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20g is independently -N(R ²⁴ )C(O)OR ²⁵ . In embodiments of the formulae above, each R ^20g is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, each R ^20g is independently -N(R ²⁴ )S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -C(O)R ²¹ . In embodiments of the formulae above, each R ^20g is independently -S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -S(O) ₂ N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20g is independently -OCH ₂ C(O)OR ²² . In embodiments of the formulae above, each R ^20g is independently -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently F. In embodiments of the formulae above, each R ^20g is independently Cl. In embodiments of the formulae above, each R ^20g is independently Br. In embodiments of the formulae above, each R ^20g is independently I. In embodiments of the formulae above, each R ^20g is independently -OH. In embodiments of the formulae above, each R ^20g is independently -SH. In embodiments of the formulae above, each R ^20g is independently -NH ₂ . In embodiments of the formulae above, each R ^20g is independently =C(H) ₂ . In embodiments of the formulae above, each R ^20g is independently - C(O)OH. In embodiments of the formulae above, each R ^20g is independently -C(O)NH ₂ . In embodiments of the formulae above, each R ^20g is independently -C(O)C(O)NH ₂ . In embodiments of the formulae above, each R ^20g is independently -OC(O)NH ₂ . In embodiments of the formulae above, each R ^20g is independently -NHC(O)NH ₂ . In embodiments of the formulae above, each R ^20g is independently -NHC(O)OH. In embodiments of the formulae above, each R ^20g is independently -NHC(O)H. In embodiments of the formulae above, each R ^20g is independently - NHS(O) ₂ H. In embodiments of the formulae above, each R ^20g is independently -C(O)H. In embodiments of the formulae above, each R ^20g is independently -S(O) ₂ H. In embodiments of the formulae above, each R ^20g is independently -S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ^20g is independently -OCH ₂ C(O)OH. In embodiments of the formulae above, each R ^20g is independently -OC(O)H. [00472] In embodiments of the formulae above, each R ^20g is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C ₆ - ₁₀ aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C1- ₆ haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _{2- 7} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C1-5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _{1- 5} heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00473] In embodiments of the formulae above, each R ^20g is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _{2- 7} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20g is independently C _1- 5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00474] In embodiments of the formulae above, each R ^20g is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20g is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20g is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20g is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20g is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20g is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20g is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _1- 9heteroaryl. In embodiments of the formulae above, each R ^20g is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20g is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C1-5heteroaryl. In embodiments of the formulae above, each R ^20g is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20g is independently methyl. In embodiments of the formulae above, each R ^20g is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20g is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20g is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20g is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C ₂ - ₇ heterocycloalkyl. In embodiments of the formulae above, each R ^20g is independently phenyl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20g is independently -CH ₂ -C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20g is independently C _1- 5heteroaryl. [00475] In embodiments of the formulae above, R ^20g is independently C _3-12 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently C _{2- 11} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently C _6-12 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently C _1-11 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00476] In embodiments of the formulae above, R ^20g is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _1-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-6 alkyl-(C _{3- 12} cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-6 alkyl-(C _{1- 11} heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-3 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20g is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, R ^20g is independently =NR ²¹ . In embodiments of the formulae above, R ^20g is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, R ^20g is independently -C(O)R ²¹ . [00477] In embodiments of the formulae above, each R ^20h is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00478] In embodiments of the formulae above, each R ^20h is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently halogen. In embodiments of the formulae above, each R ^20h is independently oxo. In embodiments of the formulae above, each R ^20h is independently -CN. In embodiments of the formulae above, each R ^20h is independently -OR ²¹ . In embodiments of the formulae above, each R ^20h is independently -SR ²¹ . In embodiments of the formulae above, each R ^20h is independently -N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20h is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, each R ^20h is independently -C(O)OR ²² . In embodiments of the formulae above, each R ^20h is independently -C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20h is independently -C(O)C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20h is independently -OC(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20h is independently - N(R ²⁴ )C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20h is independently -N(R ²⁴ )C(O)OR ²⁵ . In embodiments of the formulae above, each R ^20h is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, each R ^20h is independently -N(R ²⁴ )S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -C(O)R ²¹ . In embodiments of the formulae above, each R ^20h is independently -S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -S(O) ₂ N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ^20h is independently -OCH ₂ C(O)OR ²² . In embodiments of the formulae above, each R ^20h is independently -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently F. In embodiments of the formulae above, each R ^20h is independently Cl. In embodiments of the formulae above, each R ^20h is independently Br. In embodiments of the formulae above, each R ^20h is independently I. In embodiments of the formulae above, each R ^20h is independently -OH. In embodiments of the formulae above, each R ^20h is independently -SH. In embodiments of the formulae above, each R ^20h is independently -NH ₂ . In embodiments of the formulae above, each R ^20h is independently =C(H) ₂ . In embodiments of the formulae above, each R ^20h is independently - C(O)OH. In embodiments of the formulae above, each R ^20h is independently -C(O)NH ₂ . In embodiments of the formulae above, each R ^20h is independently -C(O)C(O)NH ₂ . In embodiments of the formulae above, each R ^20h is independently -OC(O)NH ₂ . In embodiments of the formulae above, each R ^20h is independently -NHC(O)NH ₂ . In embodiments of the formulae above, each R ^20h is independently -NHC(O)OH. In embodiments of the formulae above, each R ^20h is independently -NHC(O)H. In embodiments of the formulae above, each R ^20h is independently - NHS(O) ₂ H. In embodiments of the formulae above, each R ^20h is independently -C(O)H. In embodiments of the formulae above, each R ^20h is independently -S(O) ₂ H. In embodiments of the formulae above, each R ^20h is independently -S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ^20h is independently -OCH ₂ C(O)OH. In embodiments of the formulae above, each R ^20h is independently -OC(O)H. [00479] In embodiments of the formulae above, each R ^20h is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _{2- 7} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _{1- 5} heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00480] In embodiments of the formulae above, each R ^20h is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C ₆ - ₁₀ aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _3- 7cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C ₂ - ₇ heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ^20h is independently C _{1- 5} heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00481] In embodiments of the formulae above, each R ^20h is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20h is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^20h is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ^20h is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ^20h is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ^20h is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ^20h is independently C _6-10 aryl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _{1- 9} heteroaryl. In embodiments of the formulae above, each R ^20h is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ^20h is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C1-5heteroaryl, and C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20h is independently C _1-3 alkyl. In embodiments of the formulae above, each R ^20h is independently methyl. In embodiments of the formulae above, each R ^20h is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ^20h is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ^20h is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ^20h is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _{2- 7} heterocycloalkyl. In embodiments of the formulae above, each R ^20h is independently phenyl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ^20h is independently -CH ₂ -C _1-5 heteroaryl. In embodiments of the formulae above, each R ^20h is independently C _{1- 5} heteroaryl. [00482] In embodiments of the formulae above, R ^20h is independently C _3-12 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently C _2- 11heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently C _6-12 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently C _1-11 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00483] In embodiments of the formulae above, R ^20h is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _1-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-6 alkyl-(C _3- 12cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-6 alkyl-(C _{1- 11} heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-3 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ^20h is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, R ^20h is independently =NR ²¹ . In embodiments of the formulae above, R ^20h is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, R ^20h is independently -C(O)R ²¹ . [00484] In embodiments of the formulae above, each R ²⁰ⁱ is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . [00485] In embodiments of the formulae above, each R ²⁰ⁱ is independently selected from halogen, oxo, -CN, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently halogen. In embodiments of the formulae above, each R ²⁰ⁱ is independently oxo. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CN. In embodiments of the formulae above, each R ²⁰ⁱ is independently -OR ²¹ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -SR ²¹ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ²⁰ⁱ is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -C(O)OR ²² . In embodiments of the formulae above, each R ²⁰ⁱ is independently -C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ²⁰ⁱ is independently -C(O)C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ²⁰ⁱ is independently -OC(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ²⁰ⁱ is independently - N(R ²⁴ )C(O)N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ²⁰ⁱ is independently -N(R ²⁴ )C(O)OR ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -N(R ²⁴ )S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -C(O)R ²¹ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -S(O) ₂ R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -S(O) ₂ N(R ²² )(R ²³ ). In embodiments of the formulae above, each R ²⁰ⁱ is independently -OCH ₂ C(O)OR ²² . In embodiments of the formulae above, each R ²⁰ⁱ is independently -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently F. In embodiments of the formulae above, each R ²⁰ⁱ is independently Cl. In embodiments of the formulae above, each R ²⁰ⁱ is independently Br. In embodiments of the formulae above, each R ²⁰ⁱ is independently I. In embodiments of the formulae above, each R ²⁰ⁱ is independently -OH. In embodiments of the formulae above, each R ²⁰ⁱ is independently -SH. In embodiments of the formulae above, each R ²⁰ⁱ is independently -NH ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently =C(H) ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently - C(O)OH. In embodiments of the formulae above, each R ²⁰ⁱ is independently -C(O)NH ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -C(O)C(O)NH ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -OC(O)NH ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -NHC(O)NH ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -NHC(O)OH. In embodiments of the formulae above, each R ²⁰ⁱ is independently -NHC(O)H. In embodiments of the formulae above, each R ²⁰ⁱ is independently - NHS(O) ₂ H. In embodiments of the formulae above, each R ²⁰ⁱ is independently -C(O)H. In embodiments of the formulae above, each R ²⁰ⁱ is independently -S(O) ₂ H. In embodiments of the formulae above, each R ²⁰ⁱ is independently -S(O) ₂ NH ₂ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -OCH ₂ C(O)OH. In embodiments of the formulae above, each R ²⁰ⁱ is independently -OC(O)H. [00486] In embodiments of the formulae above, each R ²⁰ⁱ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C ₆ - ₁₀ aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _{2- 9} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C ₂ - 7heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C1-5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C1-5heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00487] In embodiments of the formulae above, each R ²⁰ⁱ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-6 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-6 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-6 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _3-10 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C ₂ - ₉ heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _2-9 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _6-10 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _{6- 10} aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-9 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-3 alkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently methyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-3 alkenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-3 alkynyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _{3- 7} cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _{1- 6} alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _3-7 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-7 heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _{2- 7} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -phenyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-5 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00488] In embodiments of the formulae above, each R ²⁰ⁱ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-6 alkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _{3- 10} cycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _6-10 aryl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _6-10 aryl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _1- 9heteroaryl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-9 heteroaryl. In embodiments of the formulae above, each R ²⁰ⁱ is independently selected from C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _3-7 cycloalkyl, - CH ₂ -C _3-7 cycloalkyl, C _2-7 heterocycloalkyl, -CH ₂ -C _2-7 heterocycloalkyl, phenyl, -CH ₂ -phenyl, -CH ₂ -C _1-5 heteroaryl, and C _1-5 heteroaryl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1-3 alkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently methyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-3 alkenyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-3 alkynyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _3-7 cycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _3-7 cycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _2-7 heterocycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C ₂ - ₇ heterocycloalkyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently phenyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -phenyl. In embodiments of the formulae above, each R ²⁰ⁱ is independently -CH ₂ -C _1-5 heteroaryl. In embodiments of the formulae above, each R ²⁰ⁱ is independently C _1- 5heteroaryl. [00489] In embodiments of the formulae above, R ²⁰ⁱ is independently C _3-12 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently C _{2- 11} heterocycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently C _6-12 aryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently C _1-11 heteroaryl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . [00490] In embodiments of the formulae above, R ²⁰ⁱ is independently -C _1-6 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _1-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , - C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _1-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _1-6 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-6 alkyl-(C _{3- 12} cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-6 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-6 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-6 alkyl-(C _{1- 11} heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-3 alkyl-(C _3-12 cycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-3 alkyl-(C _2-11 heterocycloalkyl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-3 alkyl-(C _6-12 aryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, - CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C _2-3 alkyl-(C _1-11 heteroaryl) optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , - N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ . In embodiments of the formulae above, R ²⁰ⁱ is independently =C(R ^21b ) ₂ . In embodiments of the formulae above, R ²⁰ⁱ is independently =NR ²¹ . In embodiments of the formulae above, R ²⁰ⁱ is independently -N(R ²⁴ )C(O)R ²¹ . In embodiments of the formulae above, R ²⁰ⁱ is independently -C(O)R ²¹ . [00491] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ¹³ , R ¹⁴ , R ^14a , or R ¹⁵ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00492] In embodiments of the formulae above, each R ¹³ is independently hydrogen. In embodiments of the formulae above, each R ¹³ is independently C _1-6 alkyl. In embodiments of the formulae above, each R ¹³ is independently C _1-6 haloalkyl. In embodiments of the formulae above, each R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e . [00493] In embodiments of the formulae above, each R ¹⁴ is independently hydrogen. In embodiments of the formulae above, each R ¹⁴ is independently C _1-6 alkyl. In embodiments of the formulae above, each R ¹⁴ is independently C _1-6 haloalkyl. [00494] In embodiments of the formulae above, each R ^14a is independently C _1-6 alkyl. In embodiments of the formulae above, each R ^14a is independently C _1-6 haloalkyl. [00495] In embodiments of the formulae above, each R ¹⁵ is independently C _1-6 alkyl. In embodiments of the formulae above, each R ¹⁵ is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ¹⁵ is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ¹⁵ is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ¹⁵ is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ¹⁵ is independently C _6-10 aryl. In embodiments of the formulae above, each R ¹⁵ is independently C _1-9 heteroaryl. [00496] In embodiments of the formulae above, each R ¹⁵ is independently C _1-6 alkyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently C _2-6 alkenyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently C _2-6 alkynyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently C _3-10 cycloalkyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently C _2-9 heterocycloalkyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently C _6-10 aryl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently C _1- 9heteroaryl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently ethenyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently propenyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently butenyl substituted with one, two, or three R ^20f . In embodiments of the formulae above, each R ¹⁵ is independently ethenyl. In embodiments of the formulae above, each R ¹⁵ is independently propenyl. In embodiments of the formulae above, each R ¹⁵ is independently butenyl. [00497] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ²¹ , R ^21b , R ²² , R ²³ , R ²⁴ , or R ²⁵ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00498] In embodiments of the formulae above, each R ²¹ is independently hydrogen. In embodiments of the formulae above, each R ²¹ is independently C _1-6 alkyl. In embodiments of the formulae above, each R ²¹ is independently C _1-6 haloalkyl. In embodiments of the formulae above, each R ²¹ is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ²¹ is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ²¹ is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ²¹ is independently C _{2- 9} heterocycloalkyl. In embodiments of the formulae above, each R ²¹ is independently C _6-10 aryl. In embodiments of the formulae above, each R ²¹ is independently C _1-9 heteroaryl. [00499] In embodiments of the formulae above, each R ²² is independently hydrogen. In embodiments of the formulae above, each R ²² is independently C _1-6 alkyl. In embodiments of the formulae above, each R ²² is independently C _1-6 haloalkyl. In embodiments of the formulae above, each R ²² is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ²² is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ²² is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ²² is independently C ₂ - ₉ heterocycloalkyl. In embodiments of the formulae above, each R ²² is independently C _6-10 aryl. In embodiments of the formulae above, each R ²² is independently C _1-9 heteroaryl. [00500] In embodiments of the formulae above, each R ²³ is independently hydrogen. In embodiments of the formulae above, each R ²³ is independently C _1-6 alkyl. [00501] In embodiments of the formulae above, each R ²⁴ is independently hydrogen. In embodiments of the formulae above, each R ²⁴ is independently C _1-6 alkyl. [00502] In embodiments of the formulae above, each R ²⁵ is independently C _1-6 alkyl. In embodiments of the formulae above, each R ²⁵ is independently C _2-6 alkenyl. In embodiments of the formulae above, each R ²⁵ is independently C _2-6 alkynyl. In embodiments of the formulae above, each R ²⁵ is independently C _3-10 cycloalkyl. In embodiments of the formulae above, each R ²⁵ is independently C _2-9 heterocycloalkyl. In embodiments of the formulae above, each R ²⁵ is independently C _6-10 aryl. In embodiments of the formulae above, each R ²⁵ is independently C _1-9 heteroaryl. [00503] In embodiments of the formulae above, each R ^21b is independently hydrogen. In embodiments of the formulae above, each R ^21b is independently halogen. In embodiments of the formulae above, each R ^21b is independently C _1-6 alkyl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH. In embodiments of the formulae above, two R ^21b are taken together with the carbon atom to which they are attached to form C _3-10 cycloalkyl or C _2-9 heterocycloalkyl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and - OH. In embodiments of the formulae above, each R ^21b is independently C _1-6 haloalkyl. In embodiments of the formulae above, each R ^21b is independently C _2-6 alkenyl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH. In embodiments of the formulae above, each R ^21b is independently C _2-6 alkynyl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH. In embodiments of the formulae above, each R ^21b is independently C _3-10 cycloalkyl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH. In embodiments of the formulae above, each R ^21b is independently C _2-9 heterocycloalkyl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH. In embodiments of the formulae above, each R ^21b is independently C _6-10 aryl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH. In embodiments of the formulae above, each R ^21b is independently C _1- 9heteroaryl optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH. [00504] [00505] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of W ¹ , W ³ , W ^5a , W ^5b , W ⁶ , W ⁷ , W ⁸ , W ⁹ , or W ¹⁰ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00506] In embodiments of the formulae above, W ¹ is N. In embodiments of the formulae above, W ¹ is N(R ^1b ). In embodiments of the formulae above, W ¹ is C(R ¹ ). In embodiments of the formulae above, W ¹ is C(R ¹ ) ₂ . In embodiments of the formulae above, W ¹ is C(O). In embodiments of the formulae above, W ¹ is C(S). In embodiments of the formulae above, W ¹ is C(=NR ^1b ). In embodiments of the formulae above, W ¹ is N(R ^1j ). In embodiments of the formulae above, W ¹ is C(=NR ^1j ). [00507] In embodiments of the formulae above, W ² is -C(R ² )= or -CH(R ² )-. In embodiments of the formulae above, W ² is -C(R ² )=. In embodiments of the formulae above, W ² is -C(O)-. In embodiments of the formulae above, W ² is -N=. In embodiments of the formulae above, W ² is -N(R ^2b )-. In embodiments of the formulae above, W ² is -C(R ² ) ₂ - . In embodiments of the formulae above, W ² is -C(S)-. In embodiments of the formulae above, W ² is -C(=NR ^2b )-. [00508] In embodiments of the formulae above, W ² is CR ² ; R ² is -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -O-R ¹² , -N(R ¹² )(R ¹³ ), -S-R ¹² ; and R ¹² is selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, - CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d . In embodiments of the formulae above, W ² is NR ^2b ; R ^2b is -OC(O)N(R ¹² )(R ¹³ ), -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - O-R ¹² , -S-R ¹² ; and R ¹² is selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d . [00509] In embodiments of the formulae above, W ² is CR ² or CH(R ² ).In some embodiments, W ² is CR ² . In embodiments of the formulae above, W ² is C(R ² ) ₂ . In embodiments of the formulae above, W ² is NR ^2b . [00510] In embodiments of the formulae above, W ³ is N. In embodiments of the formulae above, W ³ is N(R ^3b ). In embodiments of the formulae above, W ³ is C(R ³ ). In embodiments of the formulae above, W ³ is C(R ³ )(R ^3a ). In embodiments of the formulae above, W ³ is C(O). [00511] In embodiments of the formulae above, W ^5a W ^5b is -W ^5a W ^5b -. In embodiments of the formulae above, W ^5a W ^5b is -W ^5a -W ^5b -. In embodiments of the formulae above, W ^5a W ^5b is -W ^5a =W ^5b -. In embodiments of the formulae above, W ^5a W ^5b is =W ^5a -W ^5b =. [00512] In embodiments of the formulae above, W ^5a is a bond. In embodiments of the formulae above, W ^5a is -N=. In embodiments of the formulae above, W ^5a is -N(R ^5b )-. In embodiments of the formulae above, W ^5a is -C(R ⁵ )=. In embodiments of the formulae above, W ^5a is -C(R ⁵ )(R ^5a )-. In embodiments of the formulae above, W ^5a is -C(O)-. In embodiments of the formulae above, W ^5a is -S(O)-. In embodiments of the formulae above, W ^5a is -S(O) ₂ -. In embodiments of the formulae above, W ^5a is -C(S)-. In embodiments of the formulae above, W ^5a is -C(=NR ^5b )-. In embodiments of the formulae above, W ^5b is a bond. In embodiments of the formulae above, W ^5b is -N=. In embodiments of the formulae above, W ^5b is -N(R ^5b )-. In embodiments of the formulae above, W ^5b is -C(R ⁵ )=. In embodiments of the formulae above, W ^5b is -C(R ⁵ )(R ^5a )-. In embodiments of the formulae above, W ^5b is -C(O)-. In embodiments of the formulae above, W ^5b is -S(O)-. In embodiments of the formulae above, W ^5b is -S(O) ₂ -. In embodiments of the formulae above, W ^5b is -C(S)-. In embodiments of the formulae above, W ^5b is -C(=NR ^5b )-. In embodiments of the formulae above, W ⁵ is a bond. In embodiments of the formulae above, W ⁵ is -N=. In embodiments of the formulae above, W ⁵ is -N(R ^5b )-. In embodiments of the formulae above, W ⁵ is -C(R ⁵ )=. In embodiments of the formulae above, W ⁵ is -C(R ⁵ )(R ^5a )-. In embodiments of the formulae above, W ⁵ is -C(O)-. In embodiments of the formulae above, W ⁵ is -S(O)-. In embodiments of the formulae above, W ⁵ is -S(O) ₂ -. In embodiments of the formulae above, W ⁵ is -C(S)-. In embodiments of the formulae above, W ⁵ is -C(=NR ^5b )-. [00513] In embodiments of the formulae above, W ⁶ is -N=. In embodiments of the formulae above, W ⁶ is -N(R ^6b )-. In embodiments of the formulae above, W ⁶ is -C(R ⁶ )=. In embodiments of the formulae above, W ⁶ is -C(R ⁶ )(R ^6a )-. In embodiments of the formulae above, W ⁶ is -C(O)-. In embodiments of the formulae above, W ⁶ is -S(O)-. In embodiments of the formulae above, W ⁶ is -S(O) ₂ -. In embodiments of the formulae above, W ⁶ is -C(S)-. In embodiments of the formulae above, W ⁶ is -C(=NR ^6b )-. [00514] In embodiments of the formulae above, W ⁷ is -N(R ⁷ )-. In embodiments of the formulae above, W ⁷ is - C(R ⁷ )=. In embodiments of the formulae above, W ⁷ is -C(R ⁷ )(R ^7a )-. [00515] In embodiments of the formulae above, W ⁸ is -N=. In embodiments of the formulae above, W ⁸ is -N(R ^8b )-. In embodiments of the formulae above, W ⁸ is -C(R ⁸ )=. In embodiments of the formulae above, W ⁸ is -C(R ⁸ )(R ^8a )-. In embodiments of the formulae above, W ⁸ is -C(O)-. In embodiments of the formulae above, W ⁸ is -S(O)-. In embodiments of the formulae above, W ⁸ is -S(O) ₂ -. In embodiments of the formulae above, W ⁸ is -C(S)-. In embodiments of the formulae above, W ⁸ is -C(=NR ^8b )-. [00516] In embodiments of the formulae above, W ⁹ is C(R ¹² ). In embodiments of the formulae above, W ⁹ is C. In embodiments of the formulae above, W ⁹ is N. [00517] In embodiments of the formulae above, W ¹⁰ is C(R ¹² ). In embodiments of the formulae above, W ¹⁰ is C. In embodiments of the formulae above, W ¹⁰ is N. [00518] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of W ¹⁴ , W ¹⁵ , W ¹⁶ , W ¹⁷ , W ¹⁸ , s14, s15, s16, s17, s24, s25, s26, or s27) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), and (I-6), or a pharmaceutically acceptable salt or solvate thereof. [00519] In embodiments of the formulae above, W ¹⁴ is N(R ^11c ). In embodiments of the formulae above, W ¹⁴ is C(R ^11c )(R ^11c ). In embodiments of the formulae above, W ¹⁴ is N(H). In embodiments of the formulae above, W ¹⁴ is C(H)(R ^11c ). In embodiments of the formulae above, W ¹⁴ is CH2. In embodiments of the formulae above, W ¹⁴ is C(O). In embodiments of the formulae above, W ¹⁴ is S. In embodiments of the formulae above, W ¹⁴ is O. In embodiments of the formulae above, W ¹⁴ is S(O). In embodiments of the formulae above, W ¹⁴ is S(O) ₂ . [00520] In embodiments of the formulae above, W ¹⁵ is N(R ^11c ). In embodiments of the formulae above, W ¹⁵ is C(R ^11c )(R ^11c ). In embodiments of the formulae above, W ¹⁵ is N(H). In embodiments of the formulae above, W ¹⁵ is C(H)(R ^11c ). In embodiments of the formulae above, W ¹⁵ is CH ₂ . In embodiments of the formulae above, W ¹⁵ is C(O). In embodiments of the formulae above, W ¹⁵ is S. In embodiments of the formulae above, W ¹⁵ is O. In embodiments of the formulae above, W ¹⁵ is S(O). In embodiments of the formulae above, W ¹⁵ is S(O) ₂ . [00521] In embodiments of the formulae above, W ¹⁶ is C(R ^11c )(R ^11c ). In embodiments of the formulae above, W ¹⁶ is C(H)(R ^11c ). In embodiments of the formulae above, W ¹⁶ is CH ₂ . In embodiments of the formulae above, W ¹⁶ is C(O). In embodiments of the formulae above, W ¹⁶ is S. In embodiments of the formulae above, W ¹⁶ is O. In embodiments of the formulae above, W ¹⁶ is S(O). In embodiments of the formulae above, W ¹⁶ is S(O) ₂ ; [00522] In embodiments of the formulae above, W ¹⁷ is C(R ^11c )(R ^11c ). In embodiments of the formulae above, W ¹⁷ is C(H)(R ^11c ). In embodiments of the formulae above, W ¹⁷ is CH ₂ . In embodiments of the formulae above, W ¹⁷ is C(O). In embodiments of the formulae above, W ¹⁷ is S. In embodiments of the formulae above, W ¹⁷ is O. In embodiments of the formulae above, W ¹⁷ is S(O). In embodiments of the formulae above, W ¹⁷ is S(O) ₂ . [00523] In embodiments of the formulae above, W ¹⁸ is N. In embodiments of the formulae above, W ¹⁸ is CH. In embodiments of the formulae above, W ¹⁸ is C(R ^11c ). [00524] In embodiments of the formulae above, s14 is 1. In embodiments of the formulae above, s14 is 2. In embodiments of the formulae above, s14 is 3. In embodiments of the formulae above, s14 is 4. In embodiments of the formulae above, s14 is 5. [00525] In embodiments of the formulae above, s15 is 0. In embodiments of the formulae above, s15 is 1. In embodiments of the formulae above, s15 is 2. In embodiments of the formulae above, s15 is 3. In embodiments of the formulae above, s15 is 4. In embodiments of the formulae above, s15 is 5. [00526] In embodiments of the formulae above, s16 is 1. In embodiments of the formulae above, s16 is 2. In embodiments of the formulae above, s16 is 3. [00527] In embodiments of the formulae above, s17 is 1. In embodiments of the formulae above, s17 is 2. In embodiments of the formulae above, s17 is 3. [00528] In embodiments of the formulae above, s24 is 0. In embodiments of the formulae above, s24 is 1. In embodiments of the formulae above, s24 is 2. In embodiments of the formulae above, s24 is 3. In embodiments of the formulae above, s24 is 4. In embodiments of the formulae above, s24 is 5. [00529] In embodiments of the formulae above, s25 is 0. In embodiments of the formulae above, s25 is 1. In embodiments of the formulae above, s25 is 2. In embodiments of the formulae above, s25 is 3. In embodiments of the formulae above, s25 is 4. In embodiments of the formulae above, s25 is 5. [00530] In embodiments of the formulae above, s26 is 0. In embodiments of the formulae above, s26 is 1. In embodiments of the formulae above, s26 is 2. In embodiments of the formulae above, s26 is 3. In embodiments of the formulae above, s26 is 4. In embodiments of the formulae above, s26 is 5. [00531] In embodiments of the formulae above, s27 is 0. In embodiments of the formulae above, s27 is 1. In embodiments of the formulae above, s27 is 2. In embodiments of the formulae above, s27 is 3. In embodiments of the formulae above, s27 is 4. In embodiments of the formulae above, s27 is 5. [00532] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of W ¹⁹ or s37) are applicable to compounds of Formulae (I) and (I-2), or a pharmaceutically acceptable salt or solvate thereof. [00533] In embodiments of the formulae above, s37 is 0. In embodiments of the formulae above, s37 is 1. In embodiments of the formulae above, s37 is 2. In embodiments of the formulae above, s37 is 3. [00534] In embodiments of the formulae above, W ¹⁹ is CH. In embodiments of the formulae above, W ¹⁹ is C(R ^11c ). [00535] In some embodiments, the compound is In embodiments of the immediately preceding formula, R ^6b is not hydrogen. In some embodiments, the compound is In some embodiments, the compound is . In some embodiments, the compound is In some embodiments, the compound is In some embodiments, the compound is In some embodiments, the compound is [00536] In embodiments, the formula is selected from and wherein W ¹ , W ² , W ³ , W ⁴ , W ⁵ , W ⁶ , W ⁷ , W ⁸ , R ¹ , R ^1b , R ² , R ^2b , R ³ , R ^3b , R ⁸ , R ^8b , R ¹⁰ , and R ¹⁷ are as described herein. In embodiments, the formula is selected from and wherein R ^1b , R ² , R ⁵ , R ^5a , R ⁶ , R ^6a , R ⁸ , R ^8a , R ¹⁰ , and R ¹⁷ are as described herein. In embodiments, the formula is selected from

, , , wherein W ¹ , W ² , W ³ , W ⁴ , W ⁵ , W ⁶ , W ⁷ , W ⁸ , R ¹ , R ^1b , R ² , R ^2b , R ³ , R ^3b , R ⁸ , R ^8b , R ¹⁰ , and R ¹⁷ are as described herein. In embodiments, the formula , or wherein W ¹ , W ² , W ³ , W ⁴ , W ⁵ , W ⁶ , W ⁷ , W ⁸ , R ¹ , R ^1b , R ² , R ^2b , R ³ , R ^3b , R ⁸ , R ^8b , R ¹⁰ , and R ¹⁷ are as described herein. [00537] [00538] In embodiments, the formula is selected from

, wherein W ¹ , W ² , W ³ , W ⁴ , W ⁵ , W ^5a , W ^5b , W ⁶ , W ⁷ , W ⁸ , R ¹ , R ^1a , R ^1b , R ² , R ^2a , R ^2b , R ³ , R ^3a , R ^3b , R ⁴ , R ^4a , R ^4b , R ⁵ , R ^5a , R ^5b , R ⁶ , R ^6a , R ^6b , R ⁷ , R ^7a , R ^7b , R ⁸ , R ^8a , R ^8b , R ¹⁰ , and R ¹⁷ are as described herein. [00539] In embodiments, the formula wherein W ⁵ , W ⁶ , R ^1b , R ¹⁰ , and R ¹⁷ are as described herein. [00540] In embodiments, the formula wherein W ⁵ , W ⁶ , R ² , R ⁸ , R ¹⁰ , and R ¹⁷ are as described herei [00541] In embodiments, the formula wherein W ⁵ , W ⁸ , R ² , R ¹⁰ , and R ¹⁷ are as described herein. [00542] In embodiments, the formula wherein W ⁵ , W ⁶ , W ⁸ , R ² , R ¹⁰ , and R ¹⁷ are as described herei [00543] In embodiments, the formula wherein R ^1b , R ⁵ , R ⁶ , R ¹⁰ , and R ¹⁷ are as described herein. [00544] In embodiments, the formula wherein R ² , R ⁵ , R ⁶ , R ⁸ , R ¹⁰ , and R ¹⁷ are as described herein. [00545] In embodiments, the formula wherein R ² , R ⁵ , R ⁸ , R ¹⁰ , and R ¹⁷ are as described herein. [00546] In embodiments, the formula ^{2 5 5a} wherein R , R , R , R ⁶ , R ^6a , R ⁸ , R ^8a , R ¹⁰ , and R ¹⁷ are as described herein. [00547] In embodiments, the formula wherein R ² , R ⁶ , R ⁸ , R ¹⁰ , and R ⁷ are as described herein. [00548] In embodiments, the formula ^{2 6 6a} wherein R , R , R , R ⁸ , R ^8a , R ¹⁰ , and R ⁷ are as described herein. In embodiments, the formula wherein W ⁵ , W ⁶ , W ⁸ , R ² , R ¹⁰ , and R ¹⁷ are as described herein. [00549] In an aspect is provided a compound having the formula A-L ^AB -B wherein A is a monovalent form of a compound described herein; L ^AB is a covalent linker bonded to A and B; and B is a monovalent form of a degradation enhancer. [00550] A “degradation enhancer” is a compound capable of binding a ubiquitin ligase protein (e.g., E3 ubiquitin ligase protein) or a compound capable of binding a protein that is capable of binding to a ubiquitin ligase protein to form a protein complex capable of conjugating a ubiquitin protein to a target protein. In embodiments, the degradation enhancer is capable of binding to an E3 ubiquitin ligase protein or a protein complex comprising an E3 ubiquitin ligase protein. In embodiments, the degradation enhancer is capable of binding to an E2 ubiquitin- conjugating enzyme. In embodiments, the degradation enhancer is capable of binding to a protein complex comprising an E2 ubiquitin-conjugating enzyme and an E3 ubiquitin ligase protein. [00551] In embodiments, the degradation enhancer is capable of binding a protein selected from E3A, mdm2, APC, EDD1, SOCS/BC-box/eloBC/CUL5/RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von-Hippel- Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MKRN1, CMA (chaperon-mediated autophage), SCFb-TRCP (Skip-Cullin-F box (Beta-TRCP) ubiquitin complex), b-TRCP (b-transducing repeat-containing protein), cIAP1 (cellular inhibitor of apoptosis protein 1), APC/C (anaphase-promoting complex/cyclosome), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4 ^CRBN ) ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885. [00552] In embodiments, the degradation enhancer is capable of binding a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1. [00553] In embodiments, the degradation enhancer is a compound described in Ishida and Ciulli, SLAS Discovery 2021, Vol.25(4) 484-502, which is incorporated by reference in its entirety for any purpose, for example VH032, VH101, VH298, thalidomide, bestatin, methyl bestatin, nutlin, idasanutlin, bardoxolone, bardoxolone methyl, indisulam (E7070), E7820, chloroquinoxaline sulfonamide (CQS), nimbolide, KB02, ASTX660, lenalidomide, or pomalidomide. [00554] In embodiments, the degradation enhancer is a compound described in US20180050021, WO2016146985, WO2018189554, WO2018119441, WO2018140809, WO2018119448, WO2018119357, WO2018118598, WO2018102067, WO201898280, WO201889736, WO201881530, WO201871606, WO201864589, WO201852949, WO2017223452, WO2017204445, WO2017197055, WO2017197046, WO2017180417, WO2017176958, WO201711371, WO2018226542, WO2018223909, WO2018189554, WO2016169989, WO2016146985, CN105085620B, CN106543185B, US10040804, US9938302, US10144745, US10145848, US9938264, US9632089, US9821068, US9758522, US9500653, US9765019, US8507488, US8299057, US20180298027, US20180215731, US20170065719, US20170037004, US20160272639, US20150291562, or US20140356322, which are incorporated by reference in their entirety for any purpose. [00555] In embodiments L ^AB is -L ^AB1 -L ^AB2 -L ^AB3 -L ^AB4 -L ^AB5 -; L ^AB1 , L ^AB2 , L ^AB3 , L ^AB4 , and L ^AB5 are independently a bond, -O-, -N(R ¹⁴ )-, -C(O)-, -N(R ¹⁴ )C(O)-, -C(O)N(R ¹⁴ )-, -S-, - S(O) ₂ -, -S(O)-, -S(O) ₂ N(R ¹⁴ )-, -S(O)N(R ¹⁴ )-, -N(R ¹⁴ )S(O)-, -N(R ¹⁴ )S(O) ₂ -, C _1-6 alkylene, (-O-C _1-6 alkyl) _z -, (-C _{1- 6} alkyl-O) _z -, C _2-6 alkenylene, C _2-6 alkynylene, C _1-6 haloalkylene, C _3-12 cycloalkylene, C _1-11 heterocycloalkylene, C ₆ - ₁₂ arylene, or C _1-11 heteroarylene, wherein C _1-6 alkylene, C _2-6 alkenylene, C _2-6 alkynylene, C _1-6 haloalkylene, C _{3- 12} cycloalkylene, C _1-11 heterocycloalkylene, C _6-12 arylene, or C _1-11 heteroarylene,are optionally substituted with one, two, or three R ^20j ; wherein each C _1-6 alkyl of (-O-C _1-6 alkyl) _z - and (-C _1-6 alkyl-O) _z - is optionally substituted with one, two, or three R ^20j ; z is independently an integer from 0 to 10; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20d , R ^20e , R ^20f , and R ^20j are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _{6- 10} aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; and each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl. [00556] In embodiments, L ^AB is -(O-C ₂ alkyl) _z - and z is an integer from 1 to 10. [00557] In embodiments, L ^AB is -(C ₂ alkyl-O-) _z - and z is an integer from 1 to 10. [00558] In embodiments, L ^AB is -(CH ₂ ) _zz1 L ^AB2 (CH ₂ O) _zz2 -, wherein LAB2 is a bond, a 5 or 6 membered heterocycloalkylene or heteroarylene, phenylene, -(C ₂ -C ₄ )alkynylene, -SO ₂ - or -NH-; and zz1 and zz2 are independently an integer from 0 to 10. [00559] In embodiments, L ^AB is -(CH ₂ ) _zz1 (CH ₂ O) _zz2 -, wherein zz1 and zz2 are each independently an integer from 0 to 10. [00560] In embodiments, L ^AB is a PEG linker (e.g., divalent linker of 1 to 10 ethylene glycol subunits). [00561] In embodiments, B is a monovalent form of a compound selected from

[00562] In an aspect is provided a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof: Formula (II); W ¹ is N, N(R ^1b ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1b ) each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ) Each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - ₁₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3- 12cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 5-10 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2- 11heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00563] In an aspect is provided a compound of Formula (II-1), or a pharmaceutically acceptable salt or solvate thereof: Formula (II-1); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ) each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ) Each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a W ^5b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _{3- 12} cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 5-10 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _{2- 11} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00564] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^4a ) are applicable to compounds of Formulae (II) and (II-1), or a pharmaceutically acceptable salt or solvate thereof. [00565] In embodiments, R ^4a is independently a 5 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b . In embodiments, R ^4a is independently a 6 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b . In embodiments, R ^4a is independently a 7 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b . In embodiments, R ^4a is independently a 8 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b . In embodiments, R ^4a is independently a 9 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b . In embodiments, R ^4a is independently a 10 membered spirocyclic bicyclic heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b . [00566] In embodiments, R ^4a is selected from [00567] In embodiments, R ^4a is selected from

[00568] In embodiments, R ^4a is selected from , , , [00569] In embodiments, R ^4a is selected from [00570] In embodiments, R ^4a is selected from

. [00571] In embodiments, R ^4a is selected from [00572] In embodiments, R ^4a is selected from

[00573] In embodiments, R ^4a is selected from , , [00574] In embodiments, R ^4a is selected from , , , [00575] In an aspect is provided a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof: Formula (III); W ¹ is N, N(R ^1b ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1b ) each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ) each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3- 12cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _{3- 12} cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴⁴ is a monovalent group capable of forming a covalent bond with a Ras amino acid (e.g., a mutant Ras amino acid; a mutant K-Ras amino acid; an amino acid corresponding to amino acid 12 of human K-Ras; an amino acid corresponding to amino acid 13 of human K-Ras; an amino acid of K-Ras G12D, K-Ras G12C, K-Ras G12S, K-Ras G13D, K-Ras G13C, K-Ras G13S, K-Ras G12V, K-Ras G13V; an amino acid of human K-Ras corresponding to human K-Ras G12, K-Ras G12D, K-Ras G12C, K-Ras G12S, K-Ras G13D, K-Ras G13C, K- Ras G13S, K-Ras G12V, or K-Ras G13V); each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00576] In an aspect is provided a compound of Formula (III-1), or a pharmaceutically acceptable salt or solvate thereof: Formula (III-1); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ) each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ) each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - ₉ heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3- 12cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _{3- 12} cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴⁴ is a monovalent group capable of forming a covalent bond with a Ras amino acid (e.g., a mutant Ras amino acid; a mutant K-Ras amino acid; an amino acid corresponding to amino acid 12 of human K-Ras; an amino acid corresponding to amino acid 13 of human K-Ras; an amino acid of K-Ras G12D, K-Ras G12C, K-Ras G12S, K-Ras G13D, K-Ras G13C, K-Ras G13S, K-Ras G12V, K-Ras G13V; an amino acid of human K-Ras corresponding to human K-Ras G12, K-Ras G12D, K-Ras G12C, K-Ras G12S, K-Ras G13D, K-Ras G13C, K- Ras G13S, K-Ras G12V, or K-Ras G13V); each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00577] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ⁴⁴ ) are applicable to compounds of Formulae (III) and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00578] In embodiments, R ⁴⁴ is R ⁴ (e.g., comprising the R ^4a of Formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), or (I-6), and any embodiments thereof, or comprising the R ^4a of Formula (II) or (II-1), and any embodiments thereof). In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid moiety. In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a Ras protein. In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a K-Ras protein. In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a mutant K-Ras protein. In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant K-Ras protein. In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant G12D K-Ras protein. In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant K-Ras protein. In embodiments, R ⁴⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant G13D K-Ras protein. [00579] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^4a ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00580] In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid moiety. In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a Ras protein. In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a K-Ras protein. In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a mutant K-Ras protein. In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant K- Ras protein. In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant G12D K-Ras protein. In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant K-Ras protein. In embodiments, R ⁴ is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant G13D K-Ras protein. [00581] In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid moiety. In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a Ras protein. In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a K-Ras protein. In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of an amino acid of a mutant K-Ras protein. In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant K- Ras protein. In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 12 of a mutant G12D K-Ras protein. In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant K-Ras protein. In embodiments, R ^4a is a moiety capable of forming a covalent bond with a carboxylic acid of a sidechain of amino acid 13 of a mutant G13D K-Ras protein. [00582] In an aspect is provided a compound of Formula (I-1), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-1); W ¹ , W ² , W ³ , W ⁵ , W ⁶ , W ⁷ , W ⁸ , W ⁹ , W ¹⁰ , L ¹¹ , and R ^4a are identical to the corresponding variables in Formula (I) herein, including in the aspect of Formula (I) and any and all embodiments thereof. R ¹⁰ is -L ¹¹ -R ¹¹ ; R ¹¹ is selected from a C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; R ⁴ is -L ^4’ -R ^4a ; L ^4’ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, -P(O)R ^4d O-, -CR ^4c R ^4c CR ^4c R ^4c CR ^4c R ^4c -, -OCR ^4c R ^4c CR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c CR ^4c R ^4c -, -C(O)CR ^4c R ^4c CR ^4c R ^4c -, -SCR ^4c R ^4c CR ^4c R ^4c -, - S(O) ₂ CR ^4c R ^4c CR ^4c R ^4c -, -S(O)CR ^4c R ^4c CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c O-, - CR ^4c R ^4c CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c CR ^4c R ^4c C(O)-, -CR ^4c R ^4c CR ^4c R ^4c S-, -CR ^4c R ^4c CR ^4c R ^4c S(O) ₂ -, - CR ^4c R ^4c CR ^4c R ^4c S(O)-, or -CR ^4c R ^4c CR ^4c R ^4c P(O)R ^4d -; and indicates a single or double bond such that all valences are satisfied. [00583] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ^4’ ) are applicable to compounds of Formulae (I-1), or a pharmaceutically acceptable salt or solvate thereof. [00584] In embodiments, L ^4’ is L ⁴ . In embodiments, L ^4’ is -CR ^4c R ^4c CR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is - OCR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is -N(R ^4d )CR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is -C(O)CR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is -SCR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is -S(O) ₂ CR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is -S(O)CR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is -P(O)R ^4d CR ^4c R ^4c CR ^4c R ^4c -. In embodiments, L ^4’ is - CR ^4c R ^4c CR ^4c R ^4c O-. In embodiments, L ^4’ is -CR ^4c R ^4c CR ^4c R ^4c N(R ^4d )- . In embodiments, L ^4’ is -CR ^4c R ^4c CR ^4c R ^4c C(O) -. In embodiments, L ^4’ is -CR ^4c R ^4c CR ^4c R ^4c S-. In embodiments, L ^4’ is -CR ^4c R ^4c CR ^4c R ^4c S(O) ₂ -. In embodiments, L ^4’ is -CR ^4c R ^4c CR ^4c R ^4c S(O)-. In embodiments, L ^4’ is -CR ^4c R ^4c CR ^4c R ^4c P(O)R ^4d -. [00585] In embodiments, L ^4’ is -CH ₂ CH ₂ CH ₂ -. In embodiments, L ^4’ is -OCH ₂ CH ₂ -. In embodiments, L ^4’ is - N(H)CH ₂ CH ₂ -. In embodiments, L ^4’ is -C(O)CH ₂ CH ₂ -. In embodiments, L ^4’ is -SCH ₂ CH ₂ -. In embodiments, L ^4’ is -S(O) ₂ CH ₂ CH ₂ -. In embodiments, L ^4’ is -S(O)CH ₂ CH ₂ -. In embodiments, L ^4’ is -P(O)(CH ₃ )CH ₂ CH ₂ -. In embodiments, L ^4’ is - CH ₂ CH ₂ O-. In embodiments, L ^4’ is -CH ₂ CH ₂ N(H)- . In embodiments, L ^4’ is -CH ₂ CH ₂ C(O) -. In embodiments, L ^4’ is -CH ₂ CH ₂ S-. In embodiments, L ^4’ is -CH ₂ CH ₂ S(O) ₂ -. In embodiments, L ^4’ is -CH ₂ CH ₂ S(O)-. In embodiments, L ^4’ is -CH ₂ CH ₂ P(O)(CH ₃ )-. [00586] The individual embodiments herein below, or combinations thereof, (e.g., embodiments of R ⁴ ) are applicable to compounds of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), or a pharmaceutically acceptable salt or solvate thereof. [00587] In embodiments, R ⁴ is wherein each W ¹¹ and W ¹³ are independently selected from O, S, CH, CR ^4b , CH ₂ , CHR ^4b , C(R ^4b ) ₂ , N, NH, and NR ^4b and W ¹² is independently selected from C, CH, CR ^4b , and N, wherein at least one of W ¹¹ and W ¹³ is N, NH, or NR ^4b or W ¹² is N, and wherein the ring including W ¹¹ , W ¹² , and W ¹³ is not an aromatic ring. indicates a single or double bond such that all valences are satisfied. It will be understood that when W ¹¹ is N, NH, or N ^4b , then only one, two, or three W ¹¹ may be N, NH, or N ^4b and each W ¹¹ may optionally be different and may each be independently selected from O, S, CH, CR ^4b , CH ₂ , CHR ^4b , C(R ^4b ) ₂ , N, NH, and NR ^4b with the requirement that at least one of W ¹¹ and W ¹³ is N, NH, or NR ^4b , or W ¹² is N. For example, when R ⁴ includes three W ¹¹ , one W ¹¹ may be N, a second W ¹¹ may be CR ^4b , and a third W ¹¹ may be CH ₂ . [00588] In embodiments, the compound is selected from



[00589] In embodiments, the compound is selected from [00590] In embodiments, the compound is selected from atropisomer A, atropisomer B atropisomer A, atropisomer B , atropisomer A, atropisomer B, atropisomer A, atropisomer B,

and . [00591] In embodiments, the compound is selected from , [00592] In embodiments, the compound is selected from

, and . [00593] In embodiments, the compound is selected from and Additional Embodiments [00594] Embodiment 1: A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: Formula (I); W ¹ is N, N(R ^1b ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1b ); each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ); each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - ₁₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a W ^5b ; W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, -P(O)R ^7d O-; ^{R17 is selected from} Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - 9heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(H)(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1- 6alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-10 cycloalkyl ring system, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl; wherein each of C _3-10 cycloalkyl ring system, 3-10 membered heterocycloalkyl, C _6-10 aryl, and 5-10 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{3- 12} cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1-11 heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, - CH ₂ -C _1-11 heteroaryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -CH ₂ -C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, -CH ₂ -C _1- 11heterocycloalkyl, C _6-12 aryl, -CH ₂ -C _6-12 aryl, -CH ₂ -C _1-11 heteroaryl, and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substitutents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c -, - C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, -CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, - CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, -CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, -S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, -P(O)R ^4d O-; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 3-5 membered heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; ^{each R4b is independently selected from halogen, oxo, -CN, C} 1-6 ^{alkyl, C} 2-6 ^{alkenyl, C} 2-6 ^{alkynyl, C} 3-12 ^{cycloalkyl, C} 2- 11heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _{1- 6} alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3- 12cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; ^{each R20a, R20b, R20c, R20d, R20e, R20f, R20g, R20h, and R20i are each independently selected from halogen, oxo, -CN,} C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), - C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), - OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , - N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00595] Embodiment 2: A compound of Formula (I-2), or a pharmaceutically acceptable salt or solvate thereof: Formula (I-2); W ¹ is N, N(R ^1j ), C(R ¹ ), C(R ¹ ) ₂ , C(O), C(S), or C(=NR ^1j ); each R ¹ is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; R ^1j is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20a ; W ² is N, N(R ^2b ), C(R ² ), C(R ² ) ₂ , C(O), C(S), or C(=NR ^2b ); each R ² is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -N(=R ¹⁵ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^2b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ³ is N(R ^3b ), N, C(R ³ ), C(R ³ )(R ^3a ), or C(O); R ³ and R ^3a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; R ^3b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20b ; W ⁵ is W ^5a and W ^5b are independently a bond, -N(R ^5b )-, -N=, -C(R ⁵ )=, -C(R ⁵ )(R ^5a )-, -C(O)-, -S(O)-, or -S(O) ₂ -; wherein only one of W ^5a and W ^5b may be -C(O)-, -S(O)-, or -S(O) ₂ -; each R ⁵ and each R ^5a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; R ^5b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20c ; W ⁶ is N(R ^6b ), N, C(R ⁶ ), C(R ⁶ )(R ^6a ), C(O), S(O), or S(O) ₂ ; R ⁶ and R ^6a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; R ^6b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; W ⁷ is N(R ⁷ ), C(R ⁷ ), or C(R ⁷ )(R ^7a ); R ^7a and each R ^7c are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ^7d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20e ; R ⁷ is -L ⁷ -R ¹⁷ ; L ⁷ is a bond, -O-, -N(R ^7d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^7d -, CR ^7c R ^7c , -OCR ^7c R ^7c -, -N(R ^7d )CR ^7c R ^7c -, - C(O)CR ^7c R ^7c -, -SCR ^7c R ^7c -, -S(O) ₂ CR ^7c R ^7c -, -S(O)CR ^7c R ^7c -, -P(O)R ^7d CR ^7c R ^7c -, -CR ^7c R ^7c CR ^7c R ^7c , -CR ^7c R ^7c O-, - CR ^7c R ^7c N(R ^7d )-, -CR ^7c R ^7c C(O)-, -CR ^7c R ^7c S-, -CR ^7c R ^7c S(O) ₂ -, -CR ^7c R ^7c S(O)-, -CR ^7c R ^7c P(O)R ^7d -, -N(R ^7d )C(O)-, -N(R ^7d )S(O) ₂ -, -N(R ^7d )S(O)-, -N(R ^7d )P(O)R ^7d -, -C(O)N(R ^7d )-, -S(O) ₂ N(R ^7d )-, -S(O)N(R ^7d )-, -P(O)R ^7d N(R ^7d )-, - OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^7d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^7d O-; R ¹⁷ is selected from Q ³ is N or C(R ^1d ); Q ⁴ is O, S, or N(R ^1c ); X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , - N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , - C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , - S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ ; and each R ^1c is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . W ⁸ is C(R ⁸ ), C(R ⁸ )(R ^8a ), N, N(R ^8b ), C(O), S(O), or S(O) ₂ ; R ⁸ and R ^8a are independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹³ )(R ¹² ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; R ^8b is selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, C _1-9 heteroaryl, -OR ¹² , -SR ¹² , -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; W ⁹ is C(R ¹² ), C, or N; W ¹⁰ is C(R ¹² ), C, or N; R ¹⁰ is -L ¹¹ -R ¹¹ ; L ¹¹ is a bond, -O-, -N(R ^11b )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, -N(R ^11b )CR ^11a R ^11a -, - C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, -CR ^11a R ^11a CR ^11a R ^11a , - CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, -CR ^11a R ^11a S(O)-, - CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, -C(O)N(R ^11b )-, - S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, -C(O)O-, - S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-; each R ^11a is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^11b is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1- 6alkoxy, C _1-6 haloalkoxy, C _3-6 cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 6} cycloalkyl, -CH ₂ -C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; R ¹¹ is selected from a C _3-12 cycloalkyl, 3-12 membered heterocycloalkyl, C _6-12 aryl, and 5-12 membered heteroaryl; wherein each of C _3-12 cycloalkyl, 3-12 membered heterocycloalkyl, C _6-12 aryl, and 5-12 membered heteroaryl is substituted with one R ⁴ and is optionally substituted with one or more R ^11c ; each R ^11c is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3- 12cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, - C _0-6 alkyl-(C _6-12 aryl), -C _0-6 alkyl-(C _1-11 heteroaryl), C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , - OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , - OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and - CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-12 cycloalkyl, -C _0-6 alkyl- (C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C _6-12 aryl), -C0- 6 alkyl-(C _1-11 heteroaryl), and C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; wherein two R ^11c substituents or one R ^11c and one R ⁴ that are bonded to the same or different atoms are optionally joined to form a C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl, wherein the C _3-12 cycloalkyl, C _1-11 heterocycloalkyl, C _6-12 aryl, or C _1-11 heteroaryl are optionally substituted with one, two, or three R ^20g ; R ⁴ is -L ⁴ -R ^4a ; L ⁴ is selected from a bond, -O-, -N(R ^4d )-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^4d -, CR ^4c R ^4c , -OCR ^4c R ^4c -, - N(R ^4d )CR ^4c R ^4c -, -C(O)CR ^4c R ^4c -, -SCR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c -, -S(O)CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c -, - CR ^4c R ^4c CR ^4c R ^4c , -CR ^4c R ^4c O-, -CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c C(O)-, -CR ^4c R ^4c S-, -CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c S(O)-, - CR ^4c R ^4c P(O)R ^4d -, -N(R ^4d )C(O)-, -N(R ^4d )S(O) ₂ -, -N(R ^4d )S(O)-, -N(R ^4d )P(O)R ^4d -, -C(O)N(R ^4d )-, -S(O) ₂ N(R ^4d )-, - S(O)N(R ^4d )-, -P(O)R ^4d N(R ^4d )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^4d -, -C(O)O-, -S(O) ₂ O-, -S(O)O-, - P(O)R ^4d O-, -CR ^4c R ^4c CR ^4c R ^4c CR ^4c R ^4c -, -OCR ^4c R ^4c CR ^4c R ^4c -, -N(R ^4d )CR ^4c R ^4c CR ^4c R ^4c -, -C(O)CR ^4c R ^4c CR ^4c R ^4c -, -SCR ^4c R ^4c CR ^4c R ^4c -, -S(O) ₂ CR ^4c R ^4c CR ^4c R ^4c -, -S(O)CR ^4c R ^4c CR ^4c R ^4c -, -P(O)R ^4d CR ^4c R ^4c CR ^4c R ^4c -, - CR ^4c R ^4c CR ^4c R ^4c O-, -CR ^4c R ^4c CR ^4c R ^4c N(R ^4d )-, -CR ^4c R ^4c CR ^4c R ^4c C(O)-, -CR ^4c R ^4c CR ^4c R ^4c S-, - CR ^4c R ^4c CR ^4c R ^4c S(O) ₂ -, -CR ^4c R ^4c CR ^4c R ^4c S(O)-, and -CR ^4c R ^4c CR ^4c R ^4c P(O)R ^4d -; each R ^4c is independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C ₂ - 9heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , -OC(O)R ^14a , -N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ^14a , and -N(R ¹⁴ )S(O) ₂ R ¹⁴ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4d is independently selected from hydrogen, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _{1- 6} alkoxy, C _1-6 haloalkoxy, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _{2- 9} heterocycloalkyl, -OR ¹⁴ , -SR ¹⁴ , -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), -C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), -OCH ₂ C(O)OR ¹⁴ , and -OC(O)R ^14a , wherein C _1-6 alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, and -CH ₂ -C _2-9 heterocycloalkyl, are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ¹⁴ , -SR ¹⁴ , -N(R ¹⁴ )(R ¹⁴ ), -C(O)OR ¹⁴ , -C(O)N(R ¹⁴ )(R ¹⁴ ), - C(O)C(O)N(R ¹⁴ )(R ¹⁴ ), -OC(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)N(R ¹⁴ )(R ¹⁴ ), -N(R ¹⁴ )C(O)OR ¹⁴ , -N(R ¹⁴ )C(O)R ¹⁴ , - N(R ¹⁴ )S(O) ₂ R ¹⁴ , -C(O)R ^14a , -S(O) ₂ R ¹⁴ , -S(O) ₂ N(R ¹⁴ )(R ¹⁴ ), and -OC(O)R ^14a ; each R ^4a is independently a 3-5 membered heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b ; each R ^4b is independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C ₂ - 1 ₁ heterocycloalkyl, C _6-12 aryl, C _1-11 heteroaryl, -OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , - C(O)N(R ¹² )(R ¹³ ), -C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ ), - S(=O)(=NR ¹² )N(R ¹² )(R ¹³ ), -CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), and -P(=O)(R ¹² ) ₂ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-12 aryl, and C _1-11 heteroaryl are optionally substituted with one or more R ^20h ; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, -C _0-6 alkyl- (C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C _6-12 aryl), -C _0- 6 alkyl-(C _1-11 heteroaryl), and C _1-11 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C ₆ - 1 ₂ aryl), -C _0-6 alkyl-(C _1-11 heteroaryl), and C _1-11 heteroarylare optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ^14a is independently selected from C _1-6 alkyl and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - 1 ₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20a , R ^20b , R ^20c , R ^20d , R ^20e , R ^20f , R ^20g , R ^20h , and R ²⁰ⁱ are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-12 cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, -C _0-6 alkyl-(C _6-12 aryl), -C _0-6 alkyl-(C _1-11 heteroaryl), C _1-11 heteroaryl, - OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), =C(R ^21b ) ₂ , =NR ²¹ , -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3- 12cycloalkyl, -C _0-6 alkyl-(C _3-12 cycloalkyl), C _2-11 heterocycloalkyl, -C _0-6 alkyl-(C _2-11 heterocycloalkyl), C _6-12 aryl, - C _0-6 alkyl-(C _6-12 aryl), -C _0-6 alkyl-(C _1-11 heteroaryl) and C _1-11 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _{1- 6} haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), - OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²¹ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²¹ , - S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ^21b is independently selected from hydrogen, halogen, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl, or two R ^21b are taken together with the carbon atom to which they are attached to form C _3-10 cycloalkyl or C _2-9 heterocycloalkyl; each of which is optionally substituted with one, two, or three substituents independently selected from halogen, C _1-3 alkyl, C _1-3 haloalkyl, and -OH; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl; and indicates a single or double bond such that all valences are satisfied. [00596] Embodiment 3: The compound of any one of embodiments 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein L ¹¹ is a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -P(O)R ^11b -, CR ^11a R ^11a , -OCR ^11a R ^11a -, - N(R ^11b )CR ^11a R ^11a -, -C(O)CR ^11a R ^11a -, -SCR ^11a R ^11a -, -S(O) ₂ CR ^11a R ^11a -, -S(O)CR ^11a R ^11a -, -P(O)R ^11b CR ^11a R ^11a -, - CR ^11a R ^11a CR ^11a R ^11a , -CR ^11a R ^11a O-, -CR ^11a R ^11a N(R ^11b )-, -CR ^11a R ^11a C(O)-, -CR ^11a R ^11a S-, -CR ^11a R ^11a S(O) ₂ -, - CR ^11a R ^11a S(O)-, -CR ^11a R ^11a P(O)R ^11b -, -N(R ^11b )C(O)-, -N(R ^11b )S(O) ₂ -, -N(R ^11b )S(O)-, -N(R ^11b )P(O)R ^11b -, - C(O)N(R ^11b )-, -S(O) ₂ N(R ^11b )-, -S(O)N(R ^11b )-, -P(O)R ^11b N(R ^11b )-, -OC(O)-, -OS(O) ₂ -, -OS(O)-, -OP(O)R ^11b -, - C(O)O-, -S(O) ₂ O-, -S(O)O-, or -P(O)R ^11b O-. [00597] Embodiment 4: The compound of any one of embodiments 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein L ¹¹ is selected from a bond, -O-, -NH-, -NCH ₃ -, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -S ⁺ (O-)-, - P(O)CH ₃ -, and -CH ₂ . [00598] Embodiment 5: The compound of any one of embodiments 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein L ¹¹ is selected from a bond, -O-, -C(O)-, -S-, -S(O) ₂ -, -S(O)-, -S ⁺ (O-)-, -P(O)CH ₃ -, and - CH ₂ -. [00599] Embodiment 6: The compound of any one of embodiments 1-5, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is capable of covalently modifying a Ras protein. [00600] Embodiment 7: The compound of any one of embodiments 1-6, or a pharmaceutically acceptable salt or solvate thereof, wherein L ⁴ is -C(O)-, -CR ^4c R ^4c -, -CR ^4c R ^4c C(O)-, or -N(R ^4d )C(O)-. [00601] Embodiment 8: The compound of any one of embodiments 1-6, or a pharmaceutically acceptable salt or solvate thereof, wherein L ⁴ is -C(O)-, -CH ₂ -, -CH ₂ C(O)-, or -N(H)C(O)-. [00602] Embodiment 9: The compound of any one of embodiments 1 to 6, or a pharmaceutically acceptable salt or solvate thereof, wherein L ⁴ is selected from a bond, -C(O)-, -NHC(O)-, and-C(O)NH-. [00603] Embodiment 10: The compound of any one of embodiments 1-9, or a pharmaceutically acceptable salt or solvate thereof, wherein R ^4a is independently or [00604] Embodiment 11: The compound of any one of embodiments 1-98, or a pharmaceutically acceptable salt or solvate thereof, wherein R ^4a is independently [00605] Embodiment 12: The compound of any one of embodiments 1-9, or a pharmaceutically acceptable salt or solvate thereof, wherein R ^4a is independently [00606] Embodiment 13: The compound of any one of embodiments 1-9, or a pharmaceutically acceptable salt or solvate thereof, wherein R ^4a is independently a 3 membered heterocycloalkyl comprising at least one nitrogen ring atom and optionally substituted with one, two, three, or four R ^4b . [00607] Embodiment 14: The compound of any one of embodiments 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹¹ is a 3-10 membered heterocycloalkyl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00608] Embodiment 15: The compound of any one of embodiments 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹¹ is a C _6-10 aryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00609] Embodiment 16: The compound of any one of embodiments 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹¹ is a 5-10 membered heteroaryl substituted with one R ⁴ and optionally substituted with one or more R ^11c . [00610] Embodiment 17: The compound of any one of embodiments 1 to 16, or a pharmaceutically acceptable salt or solvate thereof, wherein R ^4b is independently selected from halogen, oxo, -CN, C _1-3 alkyl, C _3-4 cycloalkyl, C ₂ - ₃ heterocycloalkyl, phenyl, C _1-4 heteroaryl, -OH, -SH, -NH ₂ , -C(O)OCH ₃ , -OC(O)NH ₂ , -C(O)CH ₃ , -S(O)CH ₃ , - OC(O)CH ₃ , -C(O)NH ₂ , -NHC(O)CH ₃ , -S(O) ₂ CH ₃ , and -S(O) ₂ NH ₂ , wherein C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _{3- 4} cycloalkyl, C _2-3 heterocycloalkyl, phenyl, and C _1-4 heteroaryl are optionally substituted with one or more R ^20h . [00611] Embodiment 18: The compound of any one of embodiments 1 to 16, or a pharmaceutically acceptable salt or solvate thereof, wherein R ^4b is independently selected from halogen, C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _{3- 4} cycloalkyl, and -S(O) ₂ CH ₃ , , wherein C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, and C _3-4 cycloalkyl are optionally substituted with one or more R ^20h . [00612] Embodiment 19: The compound of any preceding embodiment, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is selected from: Q ³ is N or C(R ^1d ); Q ⁴ is O or S; X ⁹ , X ¹⁰ , and X ¹¹ are independently C(O), C(R ^1a ), or C(R ^1a )(R ^1b ); X ¹² is C or C(R ^1a ); each R ^1a , R ^1b , R ^1d , and R ^1h are each independently selected from hydrogen, halogen, -CN, C _1-6 alkyl, C _{1- 6} haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, C _1-9 heteroaryl, - OR ¹² , -SR ¹² , -N(R ¹² )(R ¹³ ), -C(O)OR ¹² , -OC(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)N(R ¹² )(R ¹³ ), - N(R ¹⁴ )C(O)OR ¹⁵ , -N(R ¹⁴ )S(O) ₂ R ¹⁵ , -C(O)R ¹⁵ , -S(O)R ¹⁵ , -OC(O)R ¹⁵ , -C(O)N(R ¹² )(R ¹³ ), - C(O)C(O)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(O)R ¹⁵ , -S(O) ₂ R ¹⁵ , -S(O) ₂ N(R ¹² )(R ¹³ )-, S(=O)(=NH)N(R ¹² )(R ¹³ ), - CH ₂ C(O)N(R ¹² )(R ¹³ ), -CH ₂ N(R ¹⁴ )C(O)R ¹⁵ , -CH ₂ S(O) ₂ R ¹⁵ , and -CH ₂ S(O) ₂ N(R ¹² )(R ¹³ ), wherein C _{1- 6} alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ²⁰ⁱ . [00613] Embodiment 20: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is [00614] Embodiment 21: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is [00615] Embodiment 22: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is . [00616] Embodiment 23: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is [00617] Embodiment 24: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is [00618] Embodiment 25: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is [00619] Embodiment 26: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is selected from:

[00620] Embodiment 27: The compound of any one of embodiments 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is [00621] Embodiment 28: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is C(R ² ) or CH(R ² ). [00622] Embodiment 29: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is C(R ² ). [00623] Embodiment 30: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is C(O). [00624] Embodiment 31: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is N. [00625] Embodiment 32: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is N(R ^2b ). [00626] Embodiment 33: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is C(R ² ) ₂ . [00627] Embodiment 34: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is C(S). [00628] Embodiment 35: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is C(=NR ^2b ). [00629] Embodiment 36: The compound of any one of embodiments 1 to 27, or a pharmaceutically acceptable salt or solvate thereof, wherein W ² is CH(R ² ). [00630] Embodiment 37: The compound of any one of embodiments 1 to 36, or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is independently selected from , ,

[00631] Embodiment 38: The compound of any one of embodiments 1 to 36, or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is independently selected from [00632] Embodiment 39: The compound of any one of embodiments 1 to 38, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is . [00633] Embodiment 40: The compound of any one of embodiments 1 to 38, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is [00634] Embodiment 41: The compound of any one of embodiments 1 to 38, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is [00635] Embodiment 42: The compound of any one of embodiments 1 to 38, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is [00636] Embodiment 43: The compound of any one of embodiments 1 to 38, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is [00637] Embodiment 44: The compound of any one of embodiments 1 to 38, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is [00638] Embodiment 45: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is N. [00639] Embodiment 46: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is N(R ^1b ). [00640] Embodiment 47: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is C(R ¹ ). [00641] Embodiment 48: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is C(R ¹ ) ₂ . [00642] Embodiment 49: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is C(O). [00643] Embodiment 50: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is C(S). [00644] Embodiment 51: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is C(=NR ^1b ). [00645] Embodiment 52: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is N(R ^1j ). [00646] Embodiment 53: The compound of any one of embodiments 1 to 44, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹ is C(=NR ^1j ). [00647] Embodiment 54: The compound of any one of embodiments 1 to 53, or a pharmaceutically acceptable salt or solvate thereof, wherein W ³ is N. [00648] Embodiment 55: The compound of any one of embodiments 1 to 53, or a pharmaceutically acceptable salt or solvate thereof, wherein W ³ is N(R ^3b ). [00649] Embodiment 56: The compound of any one of embodiments 1 to 53, or a pharmaceutically acceptable salt or solvate thereof, wherein W ³ is C(R ³ ). [00650] Embodiment 57: The compound of any one of embodiments 1 to 53, or a pharmaceutically acceptable salt or solvate thereof, wherein W ³ is C(R ³ )(R ^3a ). [00651] Embodiment 58: The compound of any one of embodiments 1 to 53, or a pharmaceutically acceptable salt or solvate thereof, wherein W ³ is C(O). [00652] Embodiment 59: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is a bond. [00653] Embodiment 60: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is N. [00654] Embodiment 61: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is N(R ^5b ). [00655] Embodiment 62: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is C(R ⁵ ). [00656] Embodiment 63: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is C(R ⁵ )(R ^5a ). [00657] Embodiment 64: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is C(O). [00658] Embodiment 65: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is S(O). [00659] Embodiment 66: The compound of any one of embodiments 1 to 58, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5a is S(O) ₂ . [00660] Embodiment 67: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is a bond. [00661] Embodiment 68: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is N. [00662] Embodiment 69: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is N(R ^5b ). [00663] Embodiment 70: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is C(R ⁵ ). [00664] Embodiment 71: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is C(R ⁵ )(R ^5a ). [00665] Embodiment 72: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is C(O). [00666] Embodiment 73: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is S(O). [00667] Embodiment 74: The compound of any one of embodiments 1 to 66, or a pharmaceutically acceptable salt or solvate thereof, wherein W ^5b is S(O) ₂ . [00668] Embodiment 75: The compound of any one of embodiments 1 to 74, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁶ is N. [00669] Embodiment 76: The compound of any one of embodiments 1 to 74, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁶ is N(R ^6b ). [00670] Embodiment 77: The compound of any one of embodiments 1 to 74, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁶ is C(R ⁶ ). [00671] Embodiment 78: The compound of any one of embodiments 1 to 74, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁶ is C(R ⁶ )(R ^6a ). [00672] Embodiment 79: The compound of any one of embodiments 1 to 74, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁶ is C(O). [00673] Embodiment 80: The compound of any one of embodiments 1 to 74, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁶ is S(O). [00674] Embodiment 81: The compound of any one of embodiments 1 to 74, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁶ is S(O) ₂ . [00675] Embodiment 82: The compound of any one of embodiments 1 to 81, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁷ is N(R ⁷ ). [00676] Embodiment 83: The compound of any one of embodiments 1 to 81, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁷ is C(R ⁷ ). [00677] Embodiment 84: The compound of any one of embodiments 1 to 81, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁷ is C(R ⁷ )(R ^7a ). [00678] Embodiment 85: The compound of any one of embodiments 1 to 84, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁸ is N. [00679] Embodiment 86: The compound of any one of embodiments 1 to 84, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁸ is N(R ^8b ). [00680] Embodiment 87: The compound of any one of embodiments 1 to 84, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁸ is C(R ⁸ ). [00681] Embodiment 88: The compound of any one of embodiments 1 to 84, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁸ is C(R ⁸ )(R ^8a ). [00682] Embodiment 89: The compound of any one of embodiments 1 to 84, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁸ is C(O). [00683] Embodiment 90: The compound of any one of embodiments 1 to 84, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁸ is S(O). [00684] Embodiment 91: The compound of any one of embodiments 1 to 84, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁸ is S(O) ₂ . [00685] Embodiment 92: The compound of any one of embodiments 1 to 91, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁹ is C(R ¹² ). [00686] Embodiment 93: The compound of any one of embodiments 1 to 91, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁹ is C. [00687] Embodiment 94: The compound of any one of embodiments 1 to 91, or a pharmaceutically acceptable salt or solvate thereof, wherein W ⁹ is N. [00688] Embodiment 95: The compound of any one of embodiments 1 to 94, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹⁰ is C(R ¹² ). [00689] Embodiment 96: The compound of any one of embodiments 1 to 94, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹⁰ is C. [00690] Embodiment 97: The compound of any one of embodiments 1 to 94, or a pharmaceutically acceptable salt or solvate thereof, wherein W ¹⁰ is N. [00691] Embodiment 98: A compound having the formula A-L ^AB -B wherein A is a monovalent form of a compound of one of embodiments 1 to 97; L ^AB is a covalent linker bonded to A and B; and B is a monovalent form of a degradation enhancer. [00692] Embodiment 99: The compound of embodiment 98 wherein the degradation enhancer is capable of binding a protein selected from E3A, mdm2, APC, EDD1, SOCS/BC-box/eloBC/CUL5/RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von-Hippel-Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MKRN1, CMA (chaperon-mediated autophage), SCFb-TRCP (Skip-Cullin-F box (Beta-TRCP) ubiquitin complex), b-TRCP (b-transducing repeat-containing protein), cIAP1 (cellular inhibitor of apoptosis protein 1), APC/C (anaphase- promoting complex/cyclosome), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4 ^CRBN ) ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885. [00693] Embodiment 100: The compound of embodiment 98 wherein the degradation enhancer is capable of binding a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1. [00694] Embodiment 101: The compound of any one of embodiments 98 to 100, wherein L ^AB is -L ^AB1 -L ^AB2 -L ^AB3 -L ^AB4 -L ^AB5 -; L ^AB1 , L ^AB2 , L ^AB3 , L ^AB4 , and L ^AB5 are independently a bond, -O-, -N(R ¹⁴ )-, -C(O)-, -N(R ¹⁴ )C(O)-, -C(O)N(R ¹⁴ )-, -S-, - S(O) ₂ -, -S(O)-, -S(O) ₂ N(R ¹⁴ )-, -S(O)N(R ¹⁴ )-, -N(R ¹⁴ )S(O)-, -N(R ¹⁴ )S(O) ₂ -, C _1-6 alkylene, (-O-C _1-6 alkyl) _z -, (-C _{1- 6} alkyl-O) _z -, C _2-6 alkenylene, C _2-6 alkynylene, C _1-6 haloalkylene, C _3-12 cycloalkylene, C _1-11 heterocycloalkylene, C _{6- 12} arylene, or C _1-11 heteroarylene, wherein C _1-6 alkylene, C _2-6 alkenylene, C _2-6 alkynylene, C _1-6 haloalkylene, C _{3- 12} cycloalkylene, C _1-11 heterocycloalkylene, C _6-12 arylene, or C _1-11 heteroarylene,are optionally substituted with one, two, or three R ^20j ; wherein each C _1-6 alkyl of (-O-C _1-6 alkyl) _z - and (-C _1-6 alkyl-O) _z - is optionally substituted with one, two, or three R ^20j ; z is independently an integer from 0 to 10; each R ¹² is independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _{3- 10} cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20d ; each R ¹³ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; or R ¹² and R ¹³ , together with the nitrogen to which they are attached, form a C _2-9 heterocycloalkyl ring optionally substituted with one, two, or three R ^20e ; each R ¹⁴ is independently selected from hydrogen, C _1-6 alkyl, and C _1-6 haloalkyl; each R ¹⁵ is independently selected C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl, wherein C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ - ₁₀ aryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three R ^20f ; each R ^20d , R ^20e , R ^20f , and R ^20j are each independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _2-6 alkenyl, C _{2- 6} alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _6-10 aryl, -CH ₂ -C _{6- 10} aryl, -CH ₂ -C _1-9 heteroaryl, C _1-9 heteroaryl, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), - C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , - N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , -S(O) ₂ N(R ²² )(R ²³ ), -OCH ₂ C(O)OR ²² , and -OC(O)R ²⁵ , wherein C _1-6 alkyl, C _{2- 6} alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, -CH ₂ -C _3-10 cycloalkyl, C _2-9 heterocycloalkyl, -CH ₂ -C _2-9 heterocycloalkyl, C _{6- 10} aryl, -CH ₂ -C _6-10 aryl, -CH ₂ -C _1-9 heteroaryl, and C _1-9 heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 haloalkoxy, -OR ²¹ , -SR ²¹ , -N(R ²² )(R ²³ ), -C(O)OR ²² , -C(O)N(R ²² )(R ²³ ), -C(O)C(O)N(R ²² )(R ²³ ), -OC(O)N(R ²² )(R ²³ ), - N(R ²⁴ )C(O)N(R ²² )(R ²³ ), -N(R ²⁴ )C(O)OR ²⁵ , -N(R ²⁴ )C(O)R ²⁵ , -N(R ²⁴ )S(O) ₂ R ²⁵ , -C(O)R ²⁵ , -S(O) ₂ R ²⁵ , - S(O) ₂ N(R ²² )(R ²³ ), and -OC(O)R ²⁵ ; each R ²¹ is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C ₂ - ₉ heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²² is independently selected from H, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{2- 9} heterocycloalkyl, C _6-10 aryl, and C _1-9 heteroaryl; each R ²³ is independently selected from H and C _1-6 alkyl; each R ²⁴ is independently selected from H and C _1-6 alkyl; and each R ²⁵ is independently selected from C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C _{6- 10} aryl, and C _1-9 heteroaryl. [00695] Embodiment 102: The compound of any one of embodiments 98 to 101, wherein L ^AB is -(O-C ₂ alkyl) _z - and z is an integer from 1 to 10. [00696] Embodiment 103: The compound of any one of embodiments 98 to 101, wherein L ^AB is -(C ₂ alkyl-O-) _z - and z is an integer from 1 to 10. [00697] Embodiment 104: The compound of any one of embodiments 98 to 101, wherein L ^AB is - (CH ₂ ) _zz1 L ^AB2 (CH ₂ O) _zz2 -, wherein L ^AB2 is a bond, a 5 or 6 membered heterocycloalkylene or heteroarylene, phenylene, -(C ₂ -C ₄ )alkynylene, -SO ₂ - or -NH-; and zz1 and zz2 are independently an integer from 0 to 10. [00698] Embodiment 105: The compound of any one of embodiments 98 to 101, wherein L ^AB is - (CH ₂ ) _zz1 (CH ₂ O) _zz2 -, wherein zz1 and zz2 are each independently an integer from 0 to 10. [00699] Embodiment 106: The compound of any one of embodiments 98 to 101, wherein L ^AB is a PEG linker. [00700] Embodiment 107: The compound of any one of embodiments 98 to 106, wherein B is a monovalent form of a compound selected from , ,

[00701] Embodiment 108: A pharmaceutical composition comprising a compound of any one of embodiments 1 to 107, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. [00702] Embodiment 109: A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or compound of any one of embodiments 1 to 107, or a pharmaceutically acceptable salt or solvate thereof. [00703] Embodiment 110: A method of treating cancer in a subject comprising a Ras mutant protein, the method comprising: inhibiting the Ras mutant protein of said subject by administering to said subject a compound, wherein compound is characterized in that upon contacting the Ras mutant protein, said Ras mutant protein exhibits reduced Ras signaling output. [00704] Embodiment 111: The method of any one of embodiments 109 to 110, wherein the cancer is a solid tumor. [00705] Embodiment 112: The method of any one of embodiments 109 to 110, wherein the cancer is a hematological cancer. [00706] Embodiment 113: The method of any one of embodiments 109 to 110, wherein the compound is a compound of any one of embodiments 1 to 91. [00707] Embodiment 114: A method of modulating signaling output of a Ras protein, comprising contacting a Ras protein with an effective amount of a compound or compound of any one of embodiments 1 to 107, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the signaling output of the Ras protein. [00708] Embodiment 115: A method of inhibiting cell growth, comprising administering an effective amount of a compound or compound of one of embodiments 1 to 107, or a pharmaceutically acceptable salt or solvate thereof, to a cell expressing a Ras protein, thereby inhibiting growth of said cells. [00709] Embodiment 116: The method of embodiment any one of embodiments 109 to 115 comprising administering an additional agent. [00710] Embodiment 117: The method of embodiment 116, wherein the additional agent comprises (1) an inhibitor of MEK; (2) an inhibitor of epidermal growth factor receptor (EGFR) and/or of mutants thereof; (3) an immunotherapeutic agent; (4) a taxane; (5) an anti-metabolite; (6) an inhibitor of FGFR1 and/or FGFR2 and/or FGFR3 and/or of mutants thereof; (7) a mitotic kinase inhibitor; (8) an anti-angiogenic drug; (9) a topoisomerase inhibitor; (10) a platinum-containing compound; (12) an inhibitor of c-MET and/or of mutants thereof; (13) an inhibitor of BCR-ABL and/or of mutants thereof; (14) an inhibitor of ErbB2 (Her2) and/or of mutants thereof; (15) an inhibitor of AXL and/or of mutants thereof; (16) an inhibitor of NTRK1 and/or of mutants thereof; (17) an inhibitor of RET and/or of mutants thereof; (18) an inhibitor of A-Raf and/or B-Raf and/or C-Raf and/or of mutants thereof; (19) an inhibitor of ERK and/or of mutants thereof; (20) an MDM2 inhibitor; (21) an inhibitor of mTOR; (23) an inhibitor of IGF1/2 and/or of IGF1-R; (24) an inhibitor of CDK9; (25) an inhibitor of farnesyl transferase; (26) an inhibitor of SHIP pathway; (27) an inhibitor of SRC; (28) an inhibitor of JAK; (29) a PARP inhibitor, (31) a ROS1 inhibitor; (32) an inhibitor of SHP pathway, or (33) an inhibitor of Src, FLT3, HDAC, VEGFR, PDGFR, LCK, Bcr-Abl or AKT; (34) an inhibitor of KrasG12C mutant; (35) a SHC inhibitor (e.g., PP2, AID371185); (36) a GAB inhibitor; (38) a PI-3 kinase inhibitor; (39) a MARPK inhibitor; (40) CDK4/6 inhibitor; (41) MAPK inhibitor; (42) SHP2 inhibitor; (43) checkpoint immune blockade agents; (44) or SOS1 inhibitor; or (45) a SOS 2 inhibitor.. [00711] Embodiment 118: The method of embodiment 116, wherein the additional agent comprises an inhibitor of SHP2 selected from RMC-4630, ERAS-601, , , [00712] Embodiment 119: The method of embodiment 116, wherein the additional agent comprises an inhibitor of SOS selected from RMC-5845, BI-1701963, and . [00713] Embodiment 120: The method of embodiment 116, wherein the additional agent comprises an inhibitor of EGFR selected from afatinib, erlotinib, gefitinib, lapatinib, cetuximab panitumumab, osimertinib, olmutinib, and EGF-816. [00714] Embodiment 121: The method of embodiment 116, wherein the additional agent comprises an inhibitor of MEK selected from trametinib, cobimetinib, binimetinib, selumetinib, refametinib, and AZD6244. [00715] Embodiment 122: The method of embodiment 116, wherein the additional agent comprises an inhibitor of ERK selected from ulixertinib, MK-8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, and ravoxertinib. [00716] Embodiment 123: The method of embodiment 116, wherein the additional agent comprises an inhibitor of CDK4/6 selected from palbociclib, ribociclib, and abemaciclib. [00717] Embodiment 124: The method of embodiment 116, wherein the additional agent comprises an inhibitor of BRAF selected from Sorafenib, Vemurafenib, Dabrafenib, Encorafenib, regorafenib, and GDC-879. Further Forms of Compounds Disclosed Herein Isomers [00718] Furthermore, in some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein possess one or more double bonds. The compounds presented herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the corresponding mixtures thereof. In some situations, compounds exist as tautomers. The compounds described herein include all possible tautomers within the formulas described herein. In some situations, the compounds described herein possess one or more chiral centers and each center exists in the R configuration or S configuration. The compounds described herein include all diastereomeric, enantiomeric, and epimeric forms as well as the corresponding mixtures thereof. In additional embodiments of the compounds and methods provided herein, mixtures of enantiomers and/or diastereoisomers, resulting from a single preparative step, combination, or interconversion, are useful for the applications described herein. In some embodiments, the compounds described herein are prepared as optically pure enantiomers by chiral chromatographic resolution of the racemic mixture. In some embodiments, the compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers, and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are preferred (e.g., crystalline diastereomeric salts). In some embodiments, the diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and are separated by taking advantage of these dissimilarities. In some embodiments, the diastereomers are separated by chiral chromatography, or preferably, by separation/resolution techniques based upon differences in solubility. In some embodiments, the optically pure enantiomer is then recovered, along with the resolving agent, by any practical means that does not result in racemization. [00719] In some embodiments, a compound described herein, such as a compound of Formulae (I), (I-1), (I-2), (I- 3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1), is provided as a substantially pure stereoisomer. In some embodiments, the stereoisomer is provided in at least 80% enantiomeric excess, such as at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.9% enantiomeric excess. [00720] In some embodiments, the present disclosure provides an atropisomer of a compound described herein, such as a compound of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1). In some embodiments, the atropisomer is provided in enantiomeric excess. In some embodiments, the atropisomer is provided in at least 80% enantiomeric excess, such as at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.9% enantiomeric excess. In some embodiments, the compound of Formulae (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (II), (II-1), (III), and (III-1) is preferably used as a non-racemic mixture, wherein one atropisomer is present in excess of its corresponding enantiomer or epimer. Typically, such mixture will contain a mixture of the two isomers in a ratio of at least 9:1, preferably at least 19:1. In some embodiments, the atropisomer is provided in at least 96% enantiomeric excess, meaning the compound has less than 2% of the corresponding enantiomer. In some embodiments, the atropisomer is provided in at least 96% diastereomeric excess, meaning the compound has less than 2% of the corresponding diastereomer. [00721] The term “atropisomers” refers to conformational stereoisomers which occur when rotation about a single bond in the molecule is prevented, restricted, or greatly slowed as a result of steric interactions with other parts of the molecule and wherein the substituents at both ends of the single bond are asymmetrical (i.e., optical activity arises without requiring an asymmetric carbon center or stereocenter). Where the rotational barrier about the single bond is high enough, and interconversion between conformations is slow enough, separation and isolation of the isomeric species may be permitted. Atropisomers are enantiomers (or epimers) without a single asymmetric atom. Atropisomers are typically considered stable if the barrier to interconversion is high enough to permit the atropisomers to undergo little or no interconversion at room temperature for a least a week, preferably at least a year. In some embodiments, an atropisomeric compound of the disclosure does not undergo more than about 5% interconversion to its opposite atropisomer at room temperature during one week when the atropisomeric compound is in substantially pure form, which is generally a solid state. In some embodiments, an atropisomeric compound of the disclosure does not undergo more than about 5% interconversion to its opposite atropisomer at room temperature (approximately 25 °C) during one year. The present chemical entities, pharmaceutical compositions, and methods are meant to include all such possible atropisomers, including racemic mixtures, diastereomeric mixtures, epimeric mixtures, optically pure forms of single atropisomers, and intermediate mixtures. Labeled compounds [00722] In some embodiments, the compounds described herein exist in their isotopically-labeled forms. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds as pharmaceutical compositions. Thus, in some embodiments, the compounds disclosed herein include isotopically-labeled compounds, which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that are incorporated into compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, and chloride, such as ² H, ³ H, ¹³ C, ¹⁴ C, ^l5 N, ¹⁷ O, ¹⁸ O, ³¹ P, ³² P, ³⁵ S, ¹⁸ F, and ³⁶ Cl, respectively. Compounds described herein, and pharmaceutically acceptable salts, esters, solvate, hydrates, or derivatives thereof which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labeled compounds, for example those into which radioactive isotopes such as ³ H and ¹⁴ C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i. e., ³ H and carbon-14, i.e., ¹⁴ C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavy isotopes such as deuterium, i.e., ² H, produces certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements. In some embodiments, the isotopically labeled compounds, pharmaceutically acceptable salt, ester, solvate, hydrate, or derivative thereof is prepared by any suitable method. [00723] In some embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. Pharmaceutically acceptable salts [00724] In some embodiments, the compounds described herein exist as their pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts as pharmaceutical compositions. [00725] In some embodiments, the compounds described herein possess acidic or basic groups and therefore react with any of a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds described herein, or by separately reacting a purified compound in its free form with a suitable acid or base, and isolating the salt thus formed. Solvates [00726] In some embodiments, the compounds described herein exist as solvates. In some embodiments are methods of treating diseases by administering such solvates. Further described herein are methods of treating diseases by administering such solvates as pharmaceutical compositions. [00727] Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent, and, in some embodiments, are formed during the process of crystallization with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of the compounds described herein are conveniently prepared or formed during the processes described herein. By way of example only, hydrates of the compounds described herein are conveniently prepared by recrystallization from an aqueous/organic solvent mixture, using organic solvents including, but not limited to, dioxane, tetrahydrofuran, or MeOH. In addition, the compounds provided herein exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. Synthesis of Compounds [00728] In some embodiments, the synthesis of compounds described herein are accomplished using means described in the chemical literature, using the methods described herein, or by a combination thereof. In addition, solvents, temperatures and other reaction conditions presented herein may vary. [00729] In other embodiments, the starting materials and reagents used for the synthesis of the compounds described herein are synthesized or are obtained from commercial sources, such as, but not limited to, Sigma- Aldrich, FischerScientific (Fischer Chemicals), and AcrosOrganics. [00730] In further embodiments, the compounds described herein, and other related compounds having different substituents are synthesized using techniques and materials described herein as well as those that are recognized in the field, such as described, for example, in Fieser and Fieser’s Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd’s Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), Larock’s Comprehensive Organic Transformations (VCH Publishers Inc., 1989), March, Advanced Organic Chemistry 4 ^th Ed., (Wiley 1992); Carey and Sundberg, Advanced Organic Chemistry 4 ^th Ed., Vols. A and B (Plenum 2000, 2001), and Green and Wuts, Protective Groups in Organic Synthesis 3 ^rd Ed., (Wiley 1999) (all of which are incorporated by reference for such disclosure). General methods for the preparation of compound as disclosed herein may be derived from reactions and the reactions may be modified by the use of appropriate reagents and conditions, for the introduction of the various moieties found in the formulae as provided herein. In some embodiments, the following synthetic method may be utilized. [00731] In some embodiments, the compounds of the present invention exhibit one or more functional characteristics disclosed herein. For example, a subject compound binds to a Ras protein, Kras protein or a mutant form thereof. In some embodiments, a subject compound binds specifically and also inhibits a Ras protein, Kras protein or a mutant form thereof. In some embodiments, a subject compound selectively inhibits a Kras mutant relative to a wildtype Kras. In some embodiments, a subject compound selectively inhibits KrasG12D and/or KrasG12V relative to wildtype Kras. In some embodiments, the IC50 of a subject compound for a Kras mutant (e.g., including G12D) is less than about 5 µM, less than about 1 µM, less than about 50 nM, less than about 10 nM, less than about 1 nM, less than about 0.5 nM, less than about 100 pM, or less than about 50 pM, as measured in an in vitro assay known in the art or exemplified herein. [00732] In some embodiments, a subject compound of the present disclosure is capable of reducing Ras signaling output. Such reduction can be evidenced by one or more members of the following: (i) an increase in steady state level of GDP-bound Ras protein; (ii) a reduction of phosphorylated AKTs473, (iii) a reduction of phosphorylated ERKT202/y204, (iv) a reduction of phosphorylated S6S235/236, and (v) reduction (e.g., inhibition) of cell growth of Ras-driven tumor cells (e.g., those derived from a tumor cell line disclosed herein). In some cases, the reduction in Ras signaling output can be evidenced by two, three, four or all of (i)-(v) above. [00733] It shall be understood that different aspects of the invention can be appreciated individually, collectively, or in combination with each other. Various aspects of the invention described herein may be applied to any of the particular applications disclosed herein. The compositions of matter including compounds of any formulae disclosed herein in the composition section of the present disclosure may be utilized in the method section including methods of use and production disclosed herein, or vice versa. Methods [00734] The compounds described herein, or a pharmaceutically acceptable salt or solvate thereof, are Ras inhibitors capable of inhibiting a Ras protein. Ras proteins being inhibited can be Ras mutants (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) from K-Ras, H-Ras or N-Ras. The compounds, a pharmaceutically acceptable salt or solvate thereof disclosed herein, have a wide range of applications in therapeutics, diagnostics, and other biomedical research. [00735] In an aspect is provided a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof. [00736] In an aspect is provided a method of treating cancer in a subject comprising a Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) protein , comprising inhibiting the Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) protein of said subject by administering to said subject a compound, wherein compound is characterized in that upon contacting the Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) protein, said the Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) protein activity or function is inhibited (e.g., partially inhibited or completely inhibited), such that said inhibited Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) protein exhibits reduced Ras signaling output (e.g., compared to a corresponding Ras protein not contacted by the compound). [00737] In an aspect is provided a method of modulating activity of a Ras protein (e.g., K-Ras, mutant K-Ras, G12C, G12D, G12S, G1V, G13C, or G13D), comprising contacting a Ras protein with an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the activity of the Ras protein. [00738] In an aspect is provided a method of inhibiting cell growth, comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, to a cell expressing a Ras (e.g., K-Ras) protein, thereby inhibiting growth of said cells. In embodiments, the subject method comprises administering an additional agent to said cell. [00739] In embodiments, the cancer is a solid tumor. [00740] In embodiments, the cancer is a hematological cancer. [00741] In practicing any of the methods disclosed herein, the Ras target to which a subject compound binds covalently can be a Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D), including a mutant of K-Ras, H- Ras, and N-Ras. In some embodiments, the methods of treating cancer can be applied to treat a solid tumor or a hematological cancer. In some embodiments, the cancer being treated can be, without limitation, prostate cancer, brain cancer, colon cancer, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine, cancer of the esophagus, melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin’s Disease, non-Hodgkin’s lymphoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, solid tumors of childhood, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi’s sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers, combinations of said cancers, and metastatic lesions of said cancers. In some embodiments is a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, wherein the cancer is a hematological cancer. In some embodiments is a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, wherein the cancer is a hematological cancer selected from one or more of chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non- Hodgkin’s lymphoma, Hodgkin’s lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and pre-leukemia. In some embodiments is a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, wherein the cancer is one or more cancers selected from the group consisting of chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (T-ALL), B cell acute lymphoblastic leukemia (B-ALL), and/or acute lymphoblastic leukemia (ALL). [00742] Any of the treatment methods disclosed herein can be administered alone or in combination or in conjunction with another therapy or another agent. By “combination” it is meant to include (a) formulating a subject composition containing a subject compound together with another agent, and (b) using the subject composition separate from the another agent as an overall treatment regimen. By “conjunction” it is meant that the another therapy or agent is administered either simultaneously, concurrently or sequentially with a subject composition comprising a compound disclosed herein, with no specific time limits, wherein such conjunctive administration provides a therapeutic effect. [00743] In some embodiment, a subject treatment method is combined with surgery, cellular therapy, chemotherapy, radiation, and/or immunosuppressive agents. Additionally, compositions of the present disclosure can be combined with other therapeutic agents, such as other anti-cancer agents, anti-allergic agents, anti-nausea agents (or anti-emetics), pain relievers, cytoprotective agents, immunostimulants, and combinations thereof. [00744] In one embodiment, a subject treatment method is combined with a chemotherapeutic agent. [00745] Exemplary chemotherapeutic agents include an anthracycline (e.g., doxorubicin (e.g., liposomal doxorubicin)), a vinca alkaloid (e.g., vinblastine, vincristine, vindesine, vinorelbine), an alkylating agent (e.g., cyclophosphamide, decarbazine, melphalan, ifosfamide, temozolomide), an immune cell antibody (e.g., alemtuzamab, gemtuzumab, rituximab, ofatumumab, tositumomab, brentuximab), an antimetabolite (including, e.g., folic acid antagonists, pyrimidine analogs, purine analogs and adenosine deaminase inhibitors (e.g., fludarabine)), a TNFR glucocorticoid induced TNFR related protein (GITR) agonist, a proteasome inhibitor (e.g., aclacinomycin A, gliotoxin or bortezomib), an immunomodulator such as thalidomide or a thalidomide derivative (e.g., lenalidomide). Additional chemotherapeutic agents contemplated for use in combination include busulfan (Myleran®), busulfan injection (Busulfex®), cladribine (Leustatin®), cyclophosphamide (Cytoxan® or Neosar®), cytarabine, cytosine arabinoside (Cytosar-U®), cytarabine liposome injection (DepoCyt®), daunorubicin hydrochloride (Cerubidine®), daunorubicin citrate liposome injection (DaunoXome®), dexamethasone, doxorubicin hydrochloride (Adriamycin®, Rubex®), etoposide (Vepesid®), fludarabine phosphate (Fludara®), hydroxyurea (Hydrea®), Idarubicin (Idamycin®), mitoxantrone (Novantrone®), Gemtuzumab Ozogamicin (Mylotarg®), anastrozole (Arimidex®), bicalutamide (Casodex®), bleomycin sulfate (Blenoxane®), , busulfan injection (Busulfex®), capecitabine (Xeloda®), N4-pentoxycarbonyl-5-deoxy-5-fluorocytidine, carboplatin (Paraplatin®), carmustine (BiCNU®), chlorambucil (Leukeran®), cisplatin (Platinol®), , dacarbazine (DTIC-Dome®), dactinomycin (Actinomycin D, Cosmegan), dexamethasone, docetaxel (Taxotere®), 5-fluorouracil (Adrucil®, Efudex®), flutamide (Eulexin®), tezacitibine, Gemcitabine (difluorodeoxycitidine), , ifosfamide (IFEX®), irinotecan (Camptosar®), L-asparaginase (ELSPAR®), leucovorin calcium, melphalan (Alkeran®), 6-mercaptopurine (Purinethol®), methotrexate (Folex®), mitoxantrone (Novantrone®), mylotarg, paclitaxel (Taxol®), phoenix (Yttrium90/MX-DTPA), pentostatin, polifeprosan 20 with carmustine implant (Gliadel®), tamoxifen citrate (Nolvadex®), teniposide (Vumon®), 6-thioguanine, thiotepa, tirapazamine (Tirazone®), topotecan hydrochloride for injection (Hycamptin®), vinblastine (Velban®), vincristine (Oncovin®), and vinorelbine (Navelbine®). [00746] Anti-cancer agents of particular interest for combinations with a compound of the present invention include: anthracyclines; alkylating agents; antimetabolites; drugs that inhibit either the calcium dependent phosphatase calcineurin or the p70S6 kinase FK506) or inhibit the p70S6 kinase; mTOR inhibitors; immunomodulators; anthracyclines; vinca alkaloids; proteosome inhibitors; GITR agonists; protein tyrosine phosphatase inhibitors; a CDK4 kinase inhibitor; a BTK inhibitor; a MKN kinase inhibitor; a DGK kinase inhibitor; or an oncolytic virus. [00747] Exemplary antimetabolites include, without limitation, pyrimidine analogs, purine analogs and adenosine deaminase inhibitors): methotrexate (Rheumatrex®, Trexall®), 5-fluorouracil (Adrucil®, Efudex®, Fluoroplex®), floxuridine (FUDF®), cytarabine (Cytosar-U®, Tarabine PFS), 6-mercaptopurine (Puri-Nethol®)), 6-thioguanine (Thioguanine Tabloid®), fludarabine phosphate (Fludara®), pentostatin (Nipent®), pemetrexed (Alimta®), raltitrexed (Tomudex®), cladribine (Leustatin®), clofarabine (Clofarex®, Clolar®), azacitidine (Vidaza®), decitabine and gemcitabine (Gemzar®). Preferred antimetabolites include, cytarabine, clofarabine and fludarabine. [00748] Exemplary alkylating agents include, without limitation, nitrogen mustards, ethylenimine derivatives, alkyl sulfonates, nitrosoureas and triazenes): uracil mustard (Aminouracil Mustard®, Chlorethaminacil®, Demethyldopan®, Desmethyldopan®, Haemanthamine®, Nordopan®, Uracil nitrogen Mustard®, Uracillost®, Uracilmostaza®, Uramustin®, Uramustine®), chlormethine (Mustargen®), cyclophosphamide (Cytoxan®, Neosar®, Clafen®, Endoxan®, Procytox®, Revimmune™), ifosfamide (Mitoxana®), melphalan (Alkeran®), Chlorambucil (Leukeran®), pipobroman (Amedel®, Vercyte®), triethylenemelamine (Hemel®, Hexalen®, Hexastat®), triethylenethiophosphoramine, Temozolomide (Temodar®), thiotepa (Thioplex®), busulfan (Busilvex®, Myleran®), carmustine (BiCNU®), lomustine (CeeNU®), streptozocin (Zanosar®), and Dacarbazine (DTIC-Dome®). Additional exemplary alkylating agents include, without limitation, Oxaliplatin (Eloxatin®); Temozolomide (Temodar® and Temodal®); Dactinomycin (also known as actinomycin-D, Cosmegen®); Melphalan (also known as L-PAM, L-sarcolysin, and phenylalanine mustard, Alkeran®); Altretamine (also known as hexamethylmelamine (HMM), Hexalen®); Carmustine (BiCNU®); Bendamustine (Treanda®); Busulfan (Busulfex® and Myleran®); Carboplatin (Paraplatin®); Lomustine (also known as CCNU, CeeNU®); Cisplatin (also known as CDDP, Platinol® and Platinol®-AQ); Chlorambucil (Leukeran®); Cyclophosphamide (Cytoxan® and Neosar®); Dacarbazine (also known as DTIC, DIC and imidazole carboxamide, DTIC-Dome®); Altretamine (also known as hexamethylmelamine (HMM), Hexalen®); Ifosfamide (Ifex®); Prednumustine; Procarbazine (Matulane®); Mechlorethamine (also known as nitrogen mustard, mustine and mechloroethamine hydrochloride, Mustargen®); Streptozocin (Zanosar®); Thiotepa (also known as thiophosphoamide, TESPA and TSPA, Thioplex®); Cyclophosphamide (Endoxan®, Cytoxan®, Neosar®, Procytox®, Revimmune®); and Bendamustine HCl (Treanda®). [00749] In an aspect, compositions provided herein can be administered in combination with radiotherapy such as radiation. Whole body radiation may be administered at 12 Gy. A radiation dose may comprise a cumulative dose of 12 Gy to the whole body, including healthy tissues. A radiation dose may comprise from 5 Gy to 20 Gy. A radiation dose may be 5 Gy, 6 Gy, 7 Gy, 8 Gy, 9 Gy, 10 Gy, 11 Gy, 12, Gy, 13 Gy, 14 Gy, 15 Gy, 16 Gy, 17 Gy, 18 Gy, 19 Gy, or up to 20 Gy. Radiation may be whole body radiation or partial body radiation. In the case that radiation is whole body radiation it may be uniform or not uniform. For example, when radiation may not be uniform, narrower regions of a body such as the neck may receive a higher dose than broader regions such as the hips. [00750] Where desirable, an immunosuppressive agent can be used in conjunction with a subject treatment method. Exemplary immunosuppressive agents include but are not limited to cyclosporin, azathioprine, methotrexate, mycophenolate, and FK506, antibodies, or other immunoablative agents such as CAMPATH, anti-CD3 antibodies (e.g., muromonab, otelixizumab) or other antibody therapies, cytoxin, fludarabine, cyclosporin, FK506, rapamycin, mycophenolic acid, steroids, FR901228, cytokines, and irradiation, peptide vaccine, and any combination thereof. In accordance with the presently disclosed subject matter, the above-described various methods can comprise administering at least one immunomodulatory agent. In certain embodiments, the at least one immunomodulatory agent is selected from the group consisting of immunostimulatory agents, checkpoint immune blockade agents (e.g., blockade agents or inhibitors of immune checkpoint genes, such as, for example, PD-1, PD-L1, CTLA-4, IDO, TIM3, LAG3, TIGIT, BTLA, VISTA, ICOS, KIRs and CD39), radiation therapy agents, chemotherapy agents, and combinations thereof. In some embodiments, the immunostimulatory agents are selected from the group consisting of IL-12, an agonist costimulatory monoclonal antibody, and combinations thereof. In one embodiment, the immunostimulatory agent is IL-12. In some embodiments, the agonist costimulatory monoclonal antibody is selected from the group consisting of an anti-4-lBB antibody (e.g., urelumab, PF-05082566), an anti-OX40 antibody (pogalizumab, tavolixizumab, PF-04518600), an anti-ICOS antibody (BMS986226, MEDI-570, GSK3359609, JTX-2011), and combinations thereof. In one embodiment, the agonist costimulatory monoclonal antibody is an anti-4-l BB antibody. In some embodiments, the checkpoint immune blockade agents are selected from the group consisting of anti-PD-Ll antibodies (atezolizumab, avelumab, durvalumab, BMS-936559), anti-CTLA-4 antibodies (e.g., tremelimumab, ipilimumab), anti-PD-1 antibodies (e.g., pembrolizumab, nivolumab), anti-LAG3 antibodies (e.g., C9B7W, 410C9), anti-B7-H3 antibodies (e.g., DS-5573a), anti-TIM3 antibodies (e.g., F38-2E2), and combinations thereof. In one embodiment, the checkpoint immune blockade agent is an anti-PD-Ll antibody. In some cases, a compound of the present disclosure can be administered to a subject in conjunction with (e.g., before, simultaneously or following) bone marrow transplantation, T cell ablative therapy using either chemotherapy agents such as, fludarabine, external-beam radiation therapy (XRT), cyclophosphamide, or antibodies such as OKT3 or CAMPATH. In some cases, expanded cells can be administered before or following surgery. Alternatively, compositions comprising a compound described herein can be administered with immunostimulants. Immunostimulants can be vaccines, colony stimulating agents, interferons, interleukins, viruses, antigens, co- stimulatory agents, immunogenicity agents, immunomodulators, or immunotherapeutic agents. An immunostimulant can be a cytokine such as an interleukin. One or more cytokines can be introduced with modified cells provided herein. Cytokines can be utilized to boost function of modified T lymphocytes (including adoptively transferred tumor-specific cytotoxic T lymphocytes) to expand within a tumor microenvironment. In some cases, IL-2 can be used to facilitate expansion of the modified cells described herein. Cytokines such as IL-15 can also be employed. Other relevant cytokines in the field of immunotherapy can also be utilized, such as IL-2, IL-7, IL-12, IL-15, IL-21, or any combination thereof. An interleukin can be IL-2, or aldesleukin. Aldesleukin can be administered in low dose or high dose. A high dose aldesleukin regimen can involve administering aldesleukin intravenously every 8 hours, as tolerated, for up to about 14 doses at about 0.037 mg/kg (600,000 IU/kg). An immunostimulant (e.g., aldesleukin) can be administered within 24 hours after a cellular administration. An immunostimulant (e.g., aldesleukin) can be administered in as an infusion over about 15 minutes about every 8 hours for up to about 4 days after a cellular infusion. An immunostimulant (e.g., aldesleukin) can be administered at a dose from about 100,000 IU/kg, 200,000 IU/kg, 300,000 IU/kg, 400,000 IU/kg, 500,000 IU/kg, 600,000 IU/kg, 700,000 IU/kg, 800,000 IU/kg, 900,000 IU/kg, or up to about 1,000,000 IU/kg. In some cases, aldesleukin can be administered at a dose from about 100,000 IU/kg to 300,000 IU/kg, from 300,000 IU/kg to 500,000 IU/kg, from 500,000 IU/kg to 700,000 IU/kg, from 700,000 IU/kg to about 1,000,000 IU/kg. [00751] In some embodiments, any of the compounds herein that is capable of binding a Ras protein (e.g., KRAS) to modulate activity of such Ras protein may be administered in combination or in conjunction with one or more pharmacologically active agents comprising (1) an inhibitor of MEK (e.g., MEK1, MEK2) or of mutants thereof (e.g., trametinib, cobimetinib, binimetinib, selumetinib, refametinib); (2) an inhibitor of epidermal growth factor receptor (EGFR) and/or of mutants thereof (e.g., afatinib, erlotinib, gefitinib, lapatinib, cetuximab panitumumab, osimertinib, olmutinib, EGF-816); (3) an immunotherapeutic agent (e.g., checkpoint immune blockade agents, as disclosed herein); (4) a taxane (e.g., paclitaxel, docetaxel); (5) an anti-metabolite (e.g. antifolates such as methotrexate, raltitrexed, pyrimidine analogues such as 5-fluorouracil (5-FU), ribonucleoside and deoxyribonucleoside analogues, capecitabine and gemcitabine, purine and adenosine analogues such as mercaptopurine, thioguanine, cladribine and pentostatin, cytarabine (ara C), fludarabine); (6) an inhibitor of FGFR1 and/or FGFR2 and/or FGFR3 and/or of mutants thereof (e.g., nintedanib); (7) a mitotic kinase inhibitor (e.g., a CDK4/6 inhibitor, such as, for example, palbociclib, ribociclib, abemaciclib); (8) an anti-angiogenic drug (e.g., an anti-VEGF antibody, such as, for example, bevacizumab); (9) a topoisomerase inhibitor (e.g. epipodophyllotoxins such as for example etoposide and etopophos, teniposide, amsacrin, topotecan, irinotecan, mitoxantrone); (10) a platinum-containing compound (e.g. cisplatin, oxaliplatin, carboplatin); (11) an inhibitor of ALK and/or of mutants thereof (e.g. crizotinib, alectinib, entrectinib, brigatinib); (12) an inhibitor of c-MET and/or of mutants thereof (e.g., K252a, SU11274, PHA665752, PF2341066); (13) an inhibitor of BCR-ABL and/or of mutants thereof (e.g., imatinib, dasatinib, nilotinib); (14) an inhibitor of ErbB2 (Her2) and/or of mutants thereof (e.g., afatinib, lapatinib, trastuzumab, pertuzumab); (15) an inhibitor of AXL and/or of mutants thereof (e.g., R428, amuvatinib, XL-880); (16) an inhibitor of NTRK1 and/or of mutants thereof (e.g., Merestinib); (17) an inhibitor of RET and/or of mutants thereof (e.g., BLU-667, Lenvatinib); (18) an inhibitor of A-Raf and/or B-Raf and/or C-Raf and/or of mutants thereof (RAF-709, LY-3009120); (19) an inhibitor of ERK and/or of mutants thereof (e.g., ulixertinib); (20) an MDM2 inhibitor (e.g., HDM-201 , NVP-CGM097, RG-7112, MK-8242, RG-7388, SAR405838, AMG-232, DS- 3032, RG-7775, APG-115); (21) an inhibitor of mTOR (e.g., rapamycin, temsirolimus, everolimus, ridaforolimus); (22) an inhibitor of BET (e.g., I-BET 151, I-BET 762, OTX-015, TEN-010, CPI-203, CPI-0610, olionon, RVX-208, ABBC-744, LY294002, AZD5153, MT-1, MS645); (23) an inhibitor of IGF1/2 and/or of IGF1-R (e.g., xentuzumab, MEDI-573); (24) an inhibitor of CDK9 (e.g., DRB, flavopiridol, CR8, AZD 5438, purvalanol B, AT7519, dinaciclib, SNS-032); (25) an inhibitor of farnesyl transferase (e.g., tipifarnib); (26) an inhibitor of SHIP pathway including SHIP2 inhibitor, as well as SHIP1 inhibitors; (27) an inhibitor of SRC (e.g., dasatinib); (28) an inhibitor of JAK (e.g., tofacitinib); (29) a PARP inhibitor (e.g. Olaparib, Rucaparib, Niraparib, Talazoparib), (30) a BTK inhibitor (e.g. Ibrutinib, Acalabrutinib, Zanubrutinib), (31) a ROS1 inhibitor (e.g., entrectinib), (32) an inhibitor of SHP pathway including SHP2 inhibitor (e.g., 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3- dichlorophenyl)pyrazin-2-amine, as well as SHP1 inhibitors, or (33) an inhibitor of Src, FLT3, HDAC, VEGFR, PDGFR, LCK, Bcr-Abl or AKT or (34) an inhibitor of KrasG12C mutant (e.g., including but not limited to AMG510, MRTX849, and any covalent inhibitors binding to the cysteine residue 12 of Kras, the structures of these compounds are publically known)( e.g., an inhibitor of Ras G12C as described in US20180334454, US20190144444, US20150239900, US10246424, US20180086753, WO2018143315, WO2018206539, WO20191107519, WO2019141250, WO2019150305, US9862701, US20170197945, US20180086753, US10144724, US20190055211, US20190092767, US20180127396, US20180273523, US10280172, US20180319775, US20180273515, US20180282307, US20180282308, WO2019051291, WO2019213526, WO2019213516, WO2019217691, WO2019241157, WO2019217307, WO2020047192, WO2017087528, WO2018218070, WO2018218069, WO2018218071, WO2020027083, WO2020027084, WO2019215203, WO2019155399, WO2020035031, WO2014160200, WO2018195349, WO2018112240, WO2019204442, WO2019204449, WO2019104505, WO2016179558, WO2016176338, or related patents and applications, each of which is incorporated by reference in its entirety), ), (35) a SHC inhibitor (e.g., PP2, AID371185), (36) a GAB inhibitor (e.g., GAB-0001), (37) a GRB inhibitor, (38) a PI-3 kinase inhibitor (e.g., Idelalisib, Copanlisib, Duvelisib, Alpelisib, Taselisib, Perifosine, Buparlisib, Umbralisib, NVP-BEZ235-AN), (39) a MARPK inhibitor, (40) CDK4/6 (e.g., palbociclib, ribociclib, abemaciclib), or (41) MAPK inhibitor (e.g., VX-745, VX-702, RO- 4402257, SCIO-469, BIRB-796, SD-0006, PH-797804, AMG-548, LY2228820, SB-681323, GW-856553, RWJ67657, BCT-197), or (42) an inhibitor of SHP pathway including a SHP2 inhibitor, for example a SHP2 inhibitor selected from RMC-4630, ERAS-601, as well as SHP1 inhibitors.. [00752] In some embodiments, any of the compounds herein that is capable of binding a Ras protein (e.g., Kras) to modulate activity of such Ras protein may be administered in combination or in conjunction with one or more checkpoint immune blockade agents (e.g., anti-PD-1 and/or anti-PD-L1 antibody, anti-CLTA-4 antibody). In some embodiments, any of the compounds herein that is capable of binding a Ras protein (e.g., KRAS) to modulate activity of such Ras protein may be administered in combination or in conjunction with one or more pharmacologically active agents comprising an inhibitor against one or more targets selected from the group of: MEK, epidermal growth factor receptor (EGFR), FGFR1, FGFR2, FGFR3, mitotic kinase, topoisomerase, ALK, c- MET, ErbB2, AXL, NTRK1, RET, A-Raf, B-Raf, C-Raf, ERK, MDM2, mTOR, BET, IGF1/2, IGF1-R, CDK9, SHIP1, SHIP2, SHP2, SRC, JAK, PARP, BTK, FLT3, HDAC, VEGFR, PDGFR, LCK, Bcr-Abl, AKT, KrasG12C mutant, and ROS1. Where desired, the additional agent can be an inhibitor against one or more targets selected from the group of: MEK, epidermal growth factor receptor (EGFR), FGFR1, FGFR2, FGFR3, mitotic kinase, topoisomerase, ALK, c-MET, ErbB2, AXL, NTRK1, RET, A-Raf, B-Raf, C-Raf, ERK, MDM2, mTOR, BET, IGF1/2, IGF1-R, CDK9, SHP2, SRC, JAK, PARP, BTK, FLT3, HDAC, VEGFR, PDGFR, LCK, Bcr-Abl, AKT, KrasG12C mutant, and ROS1. In some embodiments, any of the compounds herein that is capable of binding a Ras protein (e.g., KRAS, mutant Ras protein) to modulate activity of such Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) may be administered in combination or in conjunction with one or more additional pharmacologically active agents comprising an inhibitor of SOS (e.g., SOS1, SOS2) or of mutants thereof. In embodiments, the additional pharmacologically active agent administered in combination or in conjunction with a compound described herein (e.g., compound capable of binding a Ras protein) is an inhibitor of SOS (e.g., SOS1, SOS2). In embodiments, the additional pharmacologically active agent administered in combination or in conjunction with a compound (e.g., compound capable of binding a Ras protein) described herein is an inhibitor of SOS (e.g., SOS1, SOS2). In embodiments, the additional pharmacologically active agent administered in combination or in conjunction with a compound (e.g., compound capable of binding a Ras protein) described herein is an inhibitor of SOS (e.g., SOS1, SOS2) selected from RMC-5845, BI-1701963 , In embodiments, the additional pharmacologically active agent administered in combination or in conjunction with a compound described herein (e.g., compound capable of binding a Ras protein) is an inhibitor of SOS (e.g., SOS1, SOS2) described in WO2021092115, WO2018172250, WO2019201848, WO2019122129, WO2018115380, WO2021127429, WO2020180768, or WO2020180770, all of which are herein incorporated by reference in their entirety for all purposes. [00753] In some embodiments, any of the compounds herein that is capable of binding a Ras protein (e.g., Kras) to modulate activity of such Ras protein may be administered in combination or in conjunction with one or more checkpoint immune blockade agents (e.g., anti-PD-1 and/or anti-PD-L1 antibody, anti-CLTA-4 antibody). [00754] In some embodiments, any of the compounds described herein that is capable of binding a Ras protein (e.g., KRAS) may be administered in combination or in conjunction with one or more pharmacologically active agents comprising an inhibitor of: (1) SOS1 or a mutant thereof (e.g., RMC-5845, BI-3406, BAY-293, BI- 1701963); (2) SHP2 or a mutant thereof (e.g., 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyr azin-2- amine, TNO155, RMC-4630, ERAS-601, JAB-3068, IACS-13909/BBP-398, SHP099, RMC-4550); (3) SHC or a mutant thereof (e.g., PP2, AID371185); (4) GAB or a mutant thereof (e.g., GAB-0001); (5) GRB or a mutant thereof; (6) JAK or a mutant thereof (e.g., tofacitinib); (7) A-RAF, B-RAF, C-RAF, or a mutant thereof (e.g., RAF- 709, LY-3009120); (8) BRAF or a mutant thereof (e.g., Sorafenib, Vemurafenib, Dabrafenib, Encorafenib, regorafenib, GDC-879); (9) MEK or a mutant thereof (e.g., trametinib, cobimetinib, binimetinib, selumetinib, refametinib, AZD6244); (10) ERK or a mutant thereof (e.g., ulixertinib, MK-8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, ravoxertinib);; (11) PI3K or a mutant thereof (e.g., Idelalisib, Copanlisib, Duvelisib, Alpelisib, Taselisib, Perifosine, Buparlisib, Umbralisib, NVP-BEZ235-AN); (12) MAPK or a mutant thereof (e.g., VX-745, VX-702, RO-4402257, SCIO-469, BIRB-796, SD-0006, PH-797804, AMG-548, LY2228820, SB-681323, GW-856553, RWJ67657, BCT-197); (13) EGFR or a mutant thereof (e.g., afatinib, erlotinib, gefitinib, lapatinib, cetuximab panitumumab, osimertinib, olmutinib, EGF-816); (14) c-MET or a mutant thereof (e.g., K252a, SU11274, PHA665752, PF2341066); (15) ALK or a mutant thereof (e.g. crizotinib, alectinib, entrectinib, brigatinib); (16) FGFR1, FGFR-2, FGFR-3, FGFR-4 or a mutant thereof (e.g., nintedanib); (17) BCR- ABL or a mutant thereof (e.g., imatinib, dasatinib, nilotinib); (18) ErbB2 (Her2) or a mutant thereof (e.g., afatinib, lapatinib, trastuzumab, pertuzumab); (19) AXL or a mutant thereof (e.g., R428, amuvatinib, XL-880); (20) NTRK1 or a mutant thereof (e.g., merestinib); (21) ROS1 or a mutant thereof (e.g., entrectinib); (22) RET or a mutant thereof (e.g., BLU-667, Lenvatinib); (23) MDM2 or a mutant thereof (e.g., HDM-201 , NVP-CGM097, RG-7112, MK-8242, RG-7388, SAR405838, AMG-232, DS-3032, RG-7775, APG-115); (24) mTOR or a mutant thereof (e.g., rapamycin, temsirolimus, everolimus, ridaforolimus); (25) BET or a mutant thereof (e.g., I-BET 151, I-BET 762, OTX-015, TEN-010, CPI-203, CPI-0610, olionon, RVX-208, ABBC-744, LY294002, AZD5153, MT-1, MS645); (26) IGF1, IGF2, IGF1R, or a mutant thereof (e.g., xentuzumab, MEDI-573); (27) CDK9 or a mutant thereof (e.g., DRB, flavopiridol, CR8, AZD 5438, purvalanol B, AT7519, dinaciclib, SNS-032); or (28) CDK4/6 (e.g., palbociclib, ribociclib, abemaciclib). [00755] In combination therapy, a compound provided herein and other anti-cancer agent(s) may be administered either simultaneously, concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the two compounds in the body of the patient. [00756] In some embodiments, the compound of the present disclosure and the other anti-cancer agent(s) are generally administered sequentially in any order by infusion or orally. The dosing regimen may vary depending upon the stage of the disease, physical fitness of the patient, safety profiles of the individual drugs, and tolerance of the individual drugs, as well as other criteria well-known to the attending physician and medical practitioner(s) administering the combination. The compound of the present invention and other anti-cancer agent(s) may be administered within minutes of each other, hours, days, or even weeks apart depending upon the particular cycle being used for treatment. In addition, the cycle could include administration of one drug more often than the other during the treatment cycle and at different doses per administration of the drug. [00757] An antibiotic can be administered to a subject as part of a therapeutic regime. An antibiotic can be administered at a therapeutically effective dose. An antibiotic can kill or inhibit growth of bacteria. An antibiotic can be a broad spectrum antibiotic that can target a wide range of bacteria. Broad spectrum antibiotics, either a 3 ^rd or 4 ^th generation, can be cephalosporin or a quinolone. An antibiotic can also be a narrow spectrum antibiotic that can target specific types of bacteria. An antibiotic can target a bacterial cell wall such as penicillins and cephalosporins. An antibiotic can target a cellular membrane such as polymyxins. An antibiotic can interfere with essential bacterial enzymes such as antibiotics: rifamycins, lipiarmycins, quinolones, and sulfonamides. An antibiotic can also be a protein synthesis inhibitor such as macrolides, lincosamides, and tetracyclines. An antibiotic can also be a cyclic lipopeptide such as daptomycin, glycylcyclines such as tigecycline, oxazolidiones such as linezolid, and lipiarmycins such as fidaxomicin. In some cases, an antibiotic can be 1 ^st generation, 2 ^nd generation, 3 ^rd generation, 4 ^th generation, or 5 ^th generation. A first-generation antibiotic can have a narrow spectrum. Examples of 1 ^st generation antibiotics can be penicillins (Penicillin G or Penicillin V), Cephalosporins (Cephazolin, Cephalothin, Cephapirin, Cephalethin, Cephradin, or Cephadroxin). In some cases, an antibiotic can be 2 ^nd generation.2 ^nd generation antibiotics can be a penicillin (Amoxicillin or Ampicillin), Cephalosporin (Cefuroxime, Cephamandole, Cephoxitin, Cephaclor, Cephrozil, Loracarbef). In some cases, an antibiotic can be 3 ^rd generation. A 3 ^rd generation antibiotic can be penicillin (carbenicillin and ticarcillin) or cephalosporin (Cephixime, Cephtriaxone, Cephotaxime, Cephtizoxime, and Cephtazidime). An antibiotic can also be a 4 ^th generation antibiotic. A 4 ^th generation antibiotic can be Cephipime. An antibiotic can also be 5 ^th generation.5 ^th generation antibiotics can be Cephtaroline or Cephtobiprole. [00758] In some cases, an anti-viral agent may be administered as part of a treatment regime. In some cases, a herpes virus prophylaxis can be administered to a subject as part of a treatment regime. A herpes virus prophylaxis can be valacyclovir (Valtrex). Valtrex can be used orally to prevent the occurrence of herpes virus infections in subjects with positive HSV serology. It can be supplied in 500 mg tablets. Valacyclovir can be administered at a therapeutically effective amount. [00759] In some cases, a treatment regime may be dosed according to a body weight of a subject. In subjects who are determined obese (BMI > 35) a practical weight may need to be utilized. BMI is calculated by: BMI = weight (kg)/ [height (m)] ² . [00760] Body weight may be calculated for men as 50 kg+2.3*(number of inches over 60 inches) or for women 45.5kg + 2.3 (number of inches over 60 inches). An adjusted body weight may be calculated for subjects who are more than 20% of their ideal body weight. An adjusted body weight may be the sum of an ideal body weight + (0.4 x (Actual body weight – ideal body weight)). In some cases, a body surface area may be utilized to calculate a dosage. A body surface area (BSA) may be calculated by: BSA (m2) =√Height (cm) ∗Weight (kg)/3600. [00761] In an aspect is provided a method of modulating activity of a Ras (e.g., K-Ras) protein, comprising contacting a Ras protein with an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the activity of the Ras (e.g., K-Ras) protein. [00762] In some embodiments, the subject method comprises administering an additional agent or therapy. [00763] In some embodiments is a method of modulating activity of a Ras protein, comprising contacting a Ras protein with an effective amount of a compound described, or a pharmaceutically acceptable salt or solvate thereof, wherein said modulating comprises inhibiting the Ras (e.g., K-Ras) protein activity. In some embodiments is a method of modulating activity of a Ras protein including Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) proteins such as K-Ras, H-Ras, and N-Ras, comprising contacting the Ras protein with an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.. [00764] In some embodiments, provided is a method of reducing Ras signaling output in a cell by contacting the cell with a compound described herein. A reduction in Ras signalling can be evidenced by one or more members of the following: (i) an increase in steady state level of GDP-bound modified protein; (ii) a reduction of phosphorylated AKTs473, (iii) a reduction of phosphorylated ERKT202/y204, (iv) a reduction of phosphorylated S6S235/236, and (v) reduction of cell growth of a tumor cell expressing a Ras mutant (e.g., G12C, G12D, G12S, G1V, G13C, or G13D) protein, and (vi) reduction in Ras interaction with a Ras-pathway signaling protein. Non- limiting examples of Ras-pathway signaling protein include SOS (including SOS1 and SOS2), RAF, SHC, SHP (including SHP1 and SHP2), MEK, MAPK, ERK, GRB, RASA1, and GNAQ. In some cases, the reduction in Ras signaling output can be evidenced by two, three, four or all of (i)-(v) above. In some embodiments, the reduction any one or more of (i)-(v) can be 0.1-fold, 0.2-fold, 0.3-fold, 0.4-fold, 0.5-fold, 0.6-fold, 0.7-fold, 0.8-fold, 0.9-fold, 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60- fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 800-fold, 900- fold, 1000-fold, 2000-fold, 3000-fold, 4000-fold, 5000-fold, or more as compared to control untreated with a subject compound. A reduction in cell growth can be demonstrated with the use of tumor cells or cell lines. A tumor cell line can be derived from a tumor in one or more tissues, e.g., pancreas, lung, ovary, biliary tract, intestine (e.g., small intestine, large intestine (i.e. colon)), endometrium, stomach, hematopoietic tissue (e.g., lymphoid tissue), etc. Examples of the tumor cell line with a K-Ras mutation may include, but are not limited to, A549 (e.g., K-Ras G12S), AGS (e.g., K-Ras G12D), ASPC1 (e.g., K-Ras G12D), Calu-6 (e.g., K-Ras Q61K), CFPAC-1 (e.g., K-Ras G12V), CL40 (e.g., K-Ras G12D), COLO678 (e.g., K-Ras G12D), COR-L23 (e.g., K-Ras G12V), DAN-G (e.g., K- Ras G12V), GP2D (e.g., K-Ras G12D), GSU (e.g., K-Ras G12F), HCT116 (e.g., K-Ras G13D), HEC1A (e.g., K- Ras G12D), HEC1B (e.g., K-Ras G12F), HEC50B (e.g., K-Ras G12F), HEYA8 (e.g., K-Ras G12D or G13D), HPAC (e.g., K-Ras G12D), HPAFII (e.g., K-Ras G12D), HUCCT1 (e.g., K-Ras G12D), KARPAS620 (e.g., K-Ras G13D), KOPN8 (e.g., K-Ras G13D), KP-3 (e.g., K-Ras G12V), KP-4 (e.g., K-Ras G12D), L3.3 (e.g., K-Ras G12D), LoVo (e.g., K-Ras G13D), LS180 (e.g., K-Ras G12D), LS513 (e.g., K-Ras G12D), MCAS (e.g., K-Ras G12D), NB4 (e.g., K-Ras A18D), NCI-H1355 (e.g., K-Ras G13C), NCI-H1573 (e.g., K-Ras G12A), NCI-H1944 (e.g., K-Ras G13D), NCI-H2009 (e.g., K-Ras G12A), NCI-H441 (e.g., K-Ras G12V), NCI-H747 (e.g., K-Ras G13D), NOMO-1 (e.g., K-Ras G12D), OV7 (e.g., K-Ras G12D), PANC0203 (e.g., K-Ras G12D), PANC0403 (e.g., K-Ras G12D), PANC0504 (e.g., K-Ras G12D), PANC0813 (e.g., K-Ras G12D), PANC1 (e.g., K-Ras G12D), Panc-10.05 (e.g., K-Ras G12D), PaTu-8902 (e.g., K-Ras G12V), PK1 (e.g., K-Ras G12D), PK45H (e.g., K-Ras G12D), PK59 (e.g., K-Ras G12D), SK-CO-1 (e.g., K-Ras G12V), SKLU1 (e.g., K-Ras G12D), SKM-1 (e.g., K-Ras K117N), SNU1 (e.g., K-Ras G12D), SNU1033 (e.g., K-Ras G12D), SNU1197 (e.g., K-Ras G12D), SNU407 (e.g., K-Ras G12D), SNU410 (e.g., K-Ras G12D), SNU601 (e.g., K-Ras G12D), SNU61 (e.g., K-Ras G12D), SNU8 (e.g., K-Ras G12D), SNU869 (e.g., K-Ras G12D), SNU-C2A (e.g., K-Ras G12D), SU.86.86 (e.g., K-Ras G12D), SUIT2 (e.g., K-Ras G12D), SW1990 (e.g., K-Ras G12D), SW403 (e.g., K-Ras G12V), SW480 (e.g., K-Ras G12V), SW620 (e.g., K-Ras G12V), SW948 (e.g., K-Ras Q61L), T3M10 (e.g., K-Ras G12D), TCC-PAN2 (e.g., K-Ras G12R), TGBC11TKB (e.g., K-Ras G12D), and MIA Pa-Ca (e.g., MIA Pa-Ca 2 (e.g., K-Ras G12C)). [00765] In an aspect is provided a modified Ras mutant protein comprising a compound described herein (or a remnant of a compound described herein wherein the remnant of said compound is modified from a stand alone compound described herein upon covalently bonding to the amino acid) covalently bonded to the amino acid corresponding to position 12 or 13 of SEQ ID No: 1. In some embodiments, such covalently bonded modified Ras mutant protein exhibits a reduced Ras signaling output (e.g., compared to a corresponding unmodified Ras mutant absent of the covalently bonded compound). In some embodiments, a modified Ras mutant protein is a K-Ras G12D mutant, an H-Ras G12D mutant, or a N-Ras G12D mutant. In some embodiments, a modified Ras mutant protein comprises an amino acid sequence selected from the group consisting of SEQ ID No.2, SEQ ID No.6, SEQ ID No.8, and a respective fragment thereof comprising the aspartate residue corresponding to position 12 of SEQ ID No: 2. In embodiments, the modified Ras mutant protein comprises a compound described herein covalently bonded to the amino acid residue corresponding to position 12 or 13 of SEQ ID No: 1, wherein the Ras mutant protein is a human protein selected from KRas G12D, KRas G12C, KRas G12S, KRas G13D, KRas G13C, and KRas G13S. In embodiments, the modified Ras mutant protein comprises a compound described herein covalently bonded to the amino acid residue corresponding to position 12 or 13 of SEQ ID No: 1, wherein the Ras mutant protein is a mammalian Ras protein (including human protein) selected from NRas G12D, NRas G12C, NRas G12S, NRas G13D, NRas G13C, and NRas G13S. In embodiments, the modified Ras mutant protein comprises a compound described herein covalently bonded to the amino acid residue corresponding to position 12 or 13 of SEQ ID No: 1, wherein the Ras mutant protein is a mammalian protein (including human protein) selected from HRas G12D, HRas G12C, HRas G12S, HRas G13D, HRas G13C, and HRas G13S. It will be understood that a compound described herein may be modified upon covalently binding an amino acid (e.g., mutant amino acid other than G) corresponding to position 12 or 13 of human KRas (e.g., SEQ ID. No: 1). A subject compound of the present disclosure encompasses a compound described herein immediately prior to covalently bonding the Ras mutant protein as well as the resulting compound covalently bonded to the modified Ras mutant protein. For example, a subject compound of the present disclosure can be covalently bonded to a mutant Ras protein to form a modified Ras mutant protein when a ring of the compound opened upon covalently bonding to the amino acid corresponding to position 12 or 13 of SEQ ID No: 1. The compound prior to and subsequent to such covalent binding are all considered a subject compound of the present invention. [00766] In embodiments of a modified Ras mutant protein described herein, the reduced Ras signaling output is evidenced by one or more a reduced output selected from the group consisting of (i) an increase in steady state level of GDP-bound modified protein; (ii) a reduction of phosphorylated AKTs473, (iii) a reduction of phosphorylated ERK T202/Y204, (iv) a reduction of phosphorylated S6 S235/236, (v) reduction of cell growth of a tumor cell expressing a Ras mutant protein (e.g., G12D, G12C, G12S, G13D, G13C, or G13S), and (vi) reduction in Ras interaction with a Ras-pathway signaling protein [00767] In embodiments, the modified Ras mutant protein described herein is formed by contacting a compound described herein with the aspartate residue of an unmodified Ras G12D mutant protein, wherein the compound comprises a moiety susceptible to reacting with a nucleophilic aspartate residue corresponding to position 12 of SEQ ID No: 2. In some embodiments, the compound comprises a staying group and a leaving group, and wherein said contacting results in release of the leaving group and formation of said modified protein. In some embodiments, the compound selectively labels the aspartate residue corresponding to position 12 of SEQ ID No.2 (a G12D mutant) relative to a valine (G12V) residue at the same position. In some embodiments, the compound selectively labels the aspartate residue as compared to (i) a serine residue of a K-Ras G12S mutant protein, said serine corresponding to residue 12 of SEQ ID NO: 4, and/or (ii) a valine residue of a K-Ras G12V mutant protein, said valine corresponding to residue 12 of SEQ ID NO: 3. In some embodiments, the compound selectively labels the aspartate residue as compared to (i) an serine residue of a K-Ras G12S mutant protein, said serine corresponding to residue 12 of SEQ ID NO: 4, and/or (ii) a valine residue of a K-Ras G12V mutant protein, said valine corresponding to residue 12 of SEQ ID NO: 3, by at least 1, 2, 3, 4, 5, 10 folds or more, when assayed under comparable conditions. In some embodiments, the compound selectively labels the aspartate residue corresponding to position 12 of SEQ ID No.2 (a G12D KRas mutant) relative to a glycine residue at the same position in wildtype KRas. [00768] In embodiments of the modified Ras mutant protein described herein, the compound contacts the aspartate residue of an unmodified Ras G12D protein corresponding to position 12 of SEQ ID No: 2 in vitro. [00769] In embodiments of the modified Ras mutant protein described herein, the compound contacts the aspartate residue of an unmodified K-Ras G12D protein corresponding to position 12 of SEQ ID No: 2 in vivo. [00770] In an aspect is provided a method of treating cancer in a subject comprising a Ras mutant protein (e.g., KRas G12D, KRas G12C, KRas G12S, KRas G13D, KRas G13C, KRas G13S, NRas G12D, NRas G12C, NRas G12S, NRas G13D, NRas G13C, NRas G13S, HRas G12D, HRas G12C, HRas G12S, HRas G13D, HRas G13C, or HRas G13S), the method comprising modifying the Ras mutant protein of said subject by administering to said subject a compound described herein, wherein the compound is characterized in that upon contacting a Ras mutant protein, said Ras mutant protein is modified covalently at a residue corresponding to reside 12 or 13 of SEQ ID No: 1, such that said modified Ras mutant protein exhibits reduced Ras signaling output (e.g., compared to a control such as an unmodified Ras mutant protein not covalently bonded with any compound such as a compound disclosed herein). [00771] In some aspects, a subject compound exhibits one or more of the following characteristics: it is capable of reacting with a mutant residue (e.g., KRas G12D, KRas G12C, KRas G12S, KRas G13D, KRas G13C, KRas G13S, NRas G12D, NRas G12C, NRas G12S, NRas G13D, NRas G13C, NRas G13S, HRas G12D, HRas G12C, HRas G12S, HRas G13D, HRas G13C, or HRas G13S) of a Ras mutant protein and covalently modify such Ras mutant and/or it comprises a moiety susceptible to reacting with a nucleophilic amino acid residue corresponding to position 12 or 13 of SEQ ID No: 1 (e.g., KRas G12D, KRas G12C, KRas G12S, KRas G13D, KRas G13C, KRas G13S, NRas G12D, NRas G12C, NRas G12S, NRas G13D, NRas G13C, NRas G13S, HRas G12D, HRas G12C, HRas G12S, HRas G13D, HRas G13C, or HRas G13S). In some embodiments, a subject compound when used to modify a Ras mutant protein, reduces the Ras protein’s signaling output. In some embodiments, a subject compound exhibits an IC50 (against a mutant Ras (e.g., KRas G12D, KRas G12C, KRas G12S, KRas G13D, KRas G13C, KRas G13S, NRas G12D, NRas G12C, NRas G12S, NRas G13D, NRas G13C, NRas G13S, HRas G12D, HRas G12C, HRas G12S, HRas G13D, HRas G13C, or HRas G13S), as ascertained by reduction of Ras::SOS1 interaction) of less than 10 uM, 5 uM, 1 uM, 500 nM, less than 100 nM, less than 50 nM, 10 nM, 5 nM, 1nM, 500 pM, 50 pM, 10 pM or less. [00772] In some embodiments, a modified Ras mutant protein disclosed herein exhibits a reduced Ras signaling output. A reduction of signaling output can be ascertained by a wide variety of methods known in the art. For example, phosphorylation of a substrate or a specific amino acid residue thereof can be detected and/or quantified one or more techniques, such as kinase activity assays, phospho-specific antibodies, Western blot, enzyme-linked immunosorbent assays (ELISA), cell-based ELISA, intracellular flow cytometry, mass spectrometry, and multi- analyte profiling. A host of readout can evidence a reduction of Ras signaling output including without limitation: (i) an increase in steady state level of GDP-bound modified protein; (ii) a reduction of phosphorylated AKTs473, (iii) a reduction of phosphorylated ERK T202/Y204, (iv) a reduction of phosphorylated S6 S235/236, and (v) reduction of cell growth of a tumor cell expressing a Ras mutant protein (e.g., KRas G12D, KRas G12C, KRas G12S, KRas G13D, KRas G13C, KRas G13S, NRas G12D, NRas G12C, NRas G12S, NRas G13D, NRas G13C, NRas G13S, HRas G12D, HRas G12C, HRas G12S, HRas G13D, HRas G13C, or HRas G13S), and (vi) reduction in Ras interaction with a Ras-pathway signaling protein. In some embodiments, a reduction is evidenced by 2, 3, 4 or more of items (i)- (vi). In some embodiments, the reduction in Ras signaling output can be evidenced by any one of (i) – (vi) as compared to control unmodified corresponding Ras proteins that is not covalently bonded to any compound disclosed herein. For example, a control Ras protein, as described herein, can be a Ras protein (e.g., wildtype or mutated) that is not complexed with any subject compound of the present disclosure. The increase in item (i) or reduction in items (ii) through (vi) can be at least about 0.1-fold, 0.2-fold, 0.3-fold, 0.4-fold, 0.5-fold, 0.6-fold, 0.7-fold, 0.8-fold, 0.9-fold, 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20- fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 800-fold, 900-fold, 1000-fold, 2000-fold, 3000-fold, 4000-fold, 5000-fold, or more as compared to the control Ras proteins. In some embodiments, a reduction in Ras interaction with a Ras-pathway signaling protein is established by a reduced interaction with SOS (including SOS1 and SOS2), RAF, SHC, SHP (including SHP1 and SHP2), MEK, MAPK, ERK, GRB, RASA1, or GNAQ. [00773] In embodiments the modified Ras mutant protein described herein is formed by contacting a compound with the aspartate residue of an unmodified Ras G12D mutant protein, wherein the compound comprises a moiety susceptible to reacting with a nucleophilic aspartate residue corresponding to position 12 of SEQ ID No: 2. Non- limiting examples of a moiety susceptible to reaction with a nucleophilic serine residue of a K-Ras G12D protein comprise an optionally substituted aziridinyl. [00774] Signaling output measured in terms of IC50 values can be obtained, a ratio of IC50 against one mutant relative to another mutant can be calculated. For instance, a selective reduction of K-Ras G12D signaling output can be evidenced by a ratio greater than one. In particular, a selective reduction of K-Ras G12D signaling relative to K- Ras G12S signaling is evidenced as the ratio of IC50 (against K-Ras G12S) to IC50 (against K-Ras G12D) is greater than 1. [00775] It will be understood that when a compound described herein selectively labels the aspartate residue of a K-Ras G12D protein compared to another K-Ras protein(s) (e.g., WT, G12S, or G12V), the compound labels the K- Ras G12D protein with greater speed or to a greater degree or by any other quantifiable measurement compared to the other K-Ras protein (e.g., WT, G12S, G12V), under similar or identical reaction conditions for the proteins being compared. In some embodiments, the greater labeling of K-Ras G12D can be 0.1-fold, 0.2-fold, 0.3-fold, 0.4- fold, 0.5-fold, 0.6-fold, 0.7-fold, 0.8-fold, 0.9-fold, 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9- fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 800-fold, 900-fold, 1000-fold, 2000-fold, 3000-fold, 4000-fold, 5000-fold, or more as compared to another K-Ras protein (e.g., WT, G12S, or G12V). In some embodiments, compounds 102- 103, 105, 107, 109-114, and 116-118 disclosed herein exhibited crosslinking to (or labelling of ) KRas G12D of greater than 5% (e.g., greater than 5%, 6%, 7%, 8%, 9%, or 10%) compared to a control (e.g., Kras G12S) within 24 hours when assayed under identical or comparable conditions. [00776] In embodiments of the modified K-Ras G12D protein described herein, the compound contacts the aspartate residue of an unmodified Ras G12D protein corresponding to position 12 of SEQ ID No: 2 in vitro, or in vivo. [00777] In embodiments, the compounds described herein, or a pharmaceutically acceptable salt or solvate thereof, are Ras modulators (including Ras inhibitors) capable of covalently modifying a Ras protein. Ras proteins being modified can be Ras G12D mutants from K-Ras, H-Ras or N-Ras. The compounds, a pharmaceutically acceptable salt or solvate thereof disclosed herein, have a wide range of applications in therapeutics, diagnostics, and other biomedical research. [00778] In an aspect is provided a method of treating cancer in a subject comprising a Ras G12D mutant protein , comprising modifying the Ras G12D mutant protein of said subject by administering to said subject a compound described herein, wherein said compound is characterized in that upon contacting the Ras G12D mutant protein, said the Ras G12D mutant protein is modified covalently at an aspartate residue corresponding to reside 12 of SEQ ID No: 2, such that said modified K-Ras G12D protein exhibits reduced Ras signaling output (e.g., compared to a corresponding unmodified Ras protein unbound to the covalent compound). [00779] In an aspect is provided a method of modulating activity of a Ras protein (e.g., K-Ras, mutant K-Ras, K- Ras G12D), comprising contacting a Ras protein with an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the activity of the Ras protein. [00780] In practicing any of the methods disclosed herein, the Ras target to which a subject compound binds covalently can be a Ras mutant (e.g., KRas G12D, KRas G12C, KRas G12S, KRas G13D, KRas G13C, KRas G13S, NRas G12D, NRas G12C, NRas G12S, NRas G13D, NRas G13C, NRas G13S, HRas G12D, HRas G12C, HRas G12S, HRas G13D, HRas G13C, or HRas G13S). Pharmaceutical compositions and methods of administration [00781] In an aspect is provided a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. [00782] The compounds described herein, or a pharmaceutically acceptable salt or solvate thereof, are administered to subjects in a biologically compatible form suitable for administration to treat or prevent diseases, disorders or conditions. Administration of the compounds described herein can be in any pharmacological form including a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, alone or in combination with a pharmaceutically acceptable carrier. [00783] In certain embodiments, the compounds described herein are administered as a pure chemical. In other embodiments, the compounds described herein are combined with a pharmaceutically suitable or acceptable carrier (also referred to herein as a pharmaceutically suitable (or acceptable) excipient, physiologically suitable (or acceptable) excipient, or physiologically suitable (or acceptable) carrier) selected on the basis of a chosen route of administration and standard pharmaceutical practice as described, for example, in Remington: The Science and Practice of Pharmacy (Gennaro, 21 ^st Ed. Mack Pub. Co., Easton, PA (2005)). [00784] Accordingly, provided herein is a pharmaceutical composition comprising at least one compound described herein, or a pharmaceutically acceptable salt, together with one or more pharmaceutically acceptable excipients. The excipient(s) (or carrier(s)) is acceptable or suitable if the excipient is compatible with the other ingredients of the composition and not deleterious to the recipient (i.e., the subject) of the composition. [00785] In some embodiments of the methods described herein, the compounds described herein are administered either alone or in combination with pharmaceutically acceptable carriers, excipients or diluents, in a pharmaceutical composition. Administration of the compounds and compositions described herein can be affected by any method that enables delivery of the compounds to the site of action. These methods include, though are not limited to delivery via enteral routes (including oral, gastric or duodenal feeding tube, rectal suppository and rectal enema), parenteral routes (injection or infusion, including intraarterial, intracardiac, intradermal, intraduodenal, intramedullary, intramuscular, intraosseous, intraperitoneal, intrathecal, intravascular, intravenous, intravitreal, epidural and subcutaneous), inhalational, transdermal, transmucosal, sublingual, buccal and topical (including epicutaneous, dermal, enema, eye drops, ear drops, intranasal, vaginal) administration, although the most suitable route may depend upon for example the condition and disorder of the recipient. By way of example only, compounds described herein can be administered locally to the area in need of treatment, by for example, local infusion during surgery, topical application such as creams or ointments, injection, catheter, or implant. The administration can also be by direct injection at the site of a diseased tissue or organ. [00786] In some embodiments of the methods described herein, pharmaceutical compositions suitable for oral administration are presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. In some embodiments, the active ingredient is presented as a bolus, electuary or paste. [00787] Pharmaceutical compositions which can be used orally include tablets, push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with binders, inert diluents, or lubricating, surface active or dispersing agents. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. In some embodiments, the tablets are coated or scored and are formulated so as to provide slow or controlled release of the active ingredient therein. All formulations for oral administration should be in dosages suitable for such administration. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In some embodiments, stabilizers are added. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or Dragee coatings for identification or to characterize different combinations of active compound doses. [00788] In some embodiments of the methods described herein, pharmaceutical compositions are formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. The compositions may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in powder form or in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, saline or sterile pyrogen-free water, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described. [00789] Pharmaceutical compositions for parenteral administration include aqueous and non-aqueous (oily) sterile injection solutions of the active compounds which may contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. [00790] Pharmaceutical compositions may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example, as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. EXAMPLES [00791] The following examples are provided for illustrative purposes only and not to limit the scope of the claims provided herein. [00792] As used herein, the following abbreviations, unless otherwise indicated, shall be understood to have the following meanings: ACN or MeCN acetonitrile AcOH acetic acid Ac acetyl BINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene Bn benzyl BOC or Boc tert-butyl carbamate i-Bu iso-butyl t-Bu tert-butyl DCM dichloromethane (CH ₂ Cl ₂ ) DIBAL-H diisobutylaluminum hydride DIPEA or DIEA diisopropylethylamine DMAP 4-(N,N-dimethylamino)pyridine DME 1,2-dimethoxyethane DMF N,N-dimethylformamide DMA N,N-dimethylacetamide DMSO dimethylsulfoxide Dppf or dppf 1,1’-bis(diphenylphosphino)ferrocene EDC or EDCI N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride eq equivalent(s) Et ethyl Et ₂ O diethyl ether EtOH ethanol EtOAc ethyl acetate HPLC high performance liquid chromatography KHMDS potassium bis(trimethylsilyl)amide NaHMDS sodium bis(trimethylsilyl)amide LiHMDS lithium bis(trimethylsilyl)amide LAH lithium aluminum anhydride LCMS liquid chromatography mass spectrometry Me methyl MeOH methanol MS mass spectroscopy Ms mesyl NMR nuclear magnetic resonance Ph phenyl iPr/i-Pr iso-propyl RP-HPLC reverse-phase high-pressure liquid chromatography RT room temperature TBS tert-butyldimethylsilyl TEA triethylamine TFA trifluoroacetic acid THF tetrahydrofuran TLC thin layer chromatography TMS trimethylsilyl TsOH/p-TsOH p-toluenesulfonic acid. [00793] Example 1: General Synthesis

[00794] Example 1b: Example Synthesis 1

[00795] Example 1c: Example Synthesis 2

[00796] Example 1d: Synthesis of Compound 442A/435A [00797] Intermediate compound numbering is restricted to the present example. Preparation of intermediate 3 [00798] To a solution of intermediate 2 (700 mg, 3.472 mmol) in dry THF (7 mL) was added t-BuOK (585 mg, 5.215 mmol). The mixture was stirred at -78 ^o C for 10 min. Then, intermediate 1 (1.262 g, 3.822 mmol) in dry THF (7 mL) was added. The mixture was stirred at -78 ^o C for 1 h. The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure to obtain intermediate 3 (1.5 g, Yield: 87 %) as a white solid. MS m/z (ESI): 494.2 [M+H]. [00799] Preparation of intermediate 5 [00800] A mixture of intermediate 3 (800 mg, 1.608 mmol), intermediate 4 (771.6 mg, 4.824 mmol,) and DIEA (626.4 mg, 4.824 mmol) in dioxane (10 ml) was stirred at 100 ^o C for 16 h. The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel column (PE/EA=1/1) to give intermediate 5 (350 mg, Yield: 35.2 %) as a white solid. MS m/z (ESI): 617.2 [M+H]. [00801] Preparation of intermediate 7 [00802] To a solution of intermediate 5 (350 mg, 0.566 mmol), intermediate 6 (343 mg, 0.849 mmol) and Cs ₂ CO ₃ (551.6 mg, 1.694 mmol) in dry toluene (10 mL) was added DPEPhosPdCl ₂ (80.5 mg, 0.112 mmol).The mixture was stirred 110 ^o C for 3 h under N2. The mixture was diluted with EtOAc (100 mL) and water (100 ml). The organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel column (PE:EA=1:1) to get a yellow solid (300 mg, Yield: 43.6 %).MS m/z (ESI): 829.2 [M+H]. [00803] Preparation of intermediate 8 [00804] To a solution of intermediate 7 (120 mg, 0.144 mmol) in dry DCM (2 mL) was added TFA (1 mL). The mixture was stirred at room temperature for 3h. The solvent was removed under reduced pressure. The reaction mixture was diluted with a.q. NaHCO ₃ (20 mL) and DCM (50 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to afford intermediate 8 (80 mg, Yield: 88%) as a yellow solid. MS m/z (ESI): 629.2 [M+H]. [00805] Preparation of compound 442A/435A [00806] To a solution of intermediate 7 (80 mg, 0.127 mmol), intermediate 9 (40.43 mg, 0.32 mmol), HOBT (34.32 mg, 0.254 mmol), and EDCI (48.69 mg, 0.254 mmol) in DMF (2 mL) was added DIEA (66.25 mg, 0.512 mmol). The mixture was stirred at 25 ^o C under nitrogen for 16 hours. The mixture was poured into water (50 mL), and the solution was extracted with ethyl acetate (50 mL x 3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by Pre-HPLC (basic) to give 435A (4.13 mg, Yield: 4.4 %)/ 442A (3.41 mg, Yield: 3.6 %) as white solid. MS m/z (ESI): 738.3 [M+H]. [00807] ¹ H NMR (400 MHz, DMSO) δ 8.54 (d, J = 7.2 Hz, 1H), 8.14 (s, 2H), 8.00 (s, 1H), 7.24 (dd, J = 8.4, 5.2 Hz, 1H), 7.21 – 7.08 (m, 1H), 5.76 (s, 1H), 5.29 (d, J = 53.6 Hz, 1H), 4.50 – 4.25 (m, 1H), 4.23 – 4.00 (m, 2H), 3.20 – 3.00 (m, 3H), 2.90 – 2.78 (m, 1H), 2.40 – 2.25 (m, 2H), 2.22 – 1.60 (m, 10H), 1.60 – 1.48 (m, 1H), 1.20 – 1.10 (m, 1H), 0.95 – 0.85 (m, 1H), 0.50 – 0.15 (m, 4H). [00808] ¹ H NMR (400 MHz, DMSO) δ 8.54 (d, J = 7.2 Hz, 1H), 8.14 (s, 2H), 8.00 (s, 1H), 7.24 (dd, J = 8.4, 5.2 Hz, 1H), 7.21 – 7.08 (m, 1H), 5.76 (s, 1H), 5.29 (d, J = 53.6 Hz, 1H), 4.50 – 4.25 (m, 1H), 4.23 – 4.00 (m, 2H), 3.20 – 3.00 (m, 3H), 2.90 – 2.78 (m, 1H), 2.40 – 2.25 (m, 2H), 2.22 – 1.60 (m, 10H), 1.60 – 1.48 (m, 1H), 1.20 – 1.10 (m, 1H), 0.95 – 0.85 (m, 1H), 0.50 – 0.15 (m, 4H). [00809] Example 1e: Synthesis of 310 [00810] Intermediate compound numbering is restricted to the present example.

[00811] Preparation of intermediate 3 [00812] To a solution of intermediate 1 (5 g, 15.25 mmol) and intermediate 2 (3.2 g, 15.25 mmol) in i-PrOH (70 ml) was added DIEA (5.9 g 45.8 mmol). The reaction mixture was stirred at 25 ^o C for 3 h. The mixture was poured into ice water (200 mL). The mixture was filtered and the solid was diluted with MeOH (150 ml). The organic solution was concentrated to dryness under reduced pressure to give intermediate 3 (5.1 g, Yield: 66 %) as a white solid. MS m/z (ESI): 505.0 [M+H]. [00813] Preparation of intermediate 5 [00814] To a solution of intermediate 3 (2 g, 3.9 mmol) and intermediate 4 (3.14 g, 19.7 mmol) in DMSO (10 ml) was added KF (1.15 g, 19.7 mmol). The reaction mixture was stirred at 120 ^o C for 12 h. The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel column (PE/EA=1/1) to give intermediate 5 (1.1 g, Yield: 45 %) as a white solid. MS m/z (ESI): 628.1 [M+H]. [00815] Preparation of intermediate 7 [00816] To a solution of intermediate 5 (400 mg, 0.64 mmol), intermediate 2 (400 mg, 0.99 mmol), and Cs ₂ CO ₃ (622 mg, 1.91 mmol) in toluene (5 mL) was added Pd(DPEPhos)Cl ₂ (92 mg, 0.13 mmol). The mixture was stirred at 110 ^o C under nitrogen for 3 hours. The mixture was poured into water (200 mL), and the solution was extracted with ethyl acetate (200 mL X 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel column (PE/EA=1/1) to give intermediate 7 (400 mg, Yield: 74.8 %) as a white solid. MS m/z (ESI): 840.4 [M+H]. [00817] Preparation of intermediate 8 [00818] To a solution of intermediate 3 (100 mg, 0.12 mmol) in DCM (2 ml) was added TFA (1 ml). The reaction mixture was stirred at 20 ^o C for 2 h. The solvent was removed under reduced pressure. The reaction mixture was diluted with a.q. NaHCO ₃ (20 mL) and DCM (50 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to afford intermediate 8 (80 mg, 95%) as a yellow solid. MS m/z (ESI): 640.1 [M+H]. [00819] ¹ H NMR (400 MHz, DMSO) δ 8.08 (s, 2H), 7.84 (s, 1H), 7.26 (dd, J = 8.4, 5.2 Hz, 1H), 7.18 – 7.09 (m, 1H), 5.27 (d, J = 54.0 Hz, 1H), 4.32 – 4.22 (m, 2H), 4.08 (d, J = 10.4 Hz, 1H), 3.97 (d, J = 2.8 Hz, 1H), 3.60 – 3.40 (m, 4H), 3.08 (d, J = 8.4 Hz, 2H), 3.01 (s, 1H), 2.85 – 2.75 (m, 1H), 2.16 – 1.50 (m, 10H). [00820] Preparation of compound 310 [00821] To a solution of intermediate 8 (70 mg, 0.11 mmol) in DMF (5 mL) was added intermediate 9 (29 mg, 0.22 mmol), HOBT(30 mg, 0.22 mmol), EDCI (63 mg, 0.33 mmol ) and DIEA (78.9 mg, 0.61 mmol ). The mixture was stirred at 25 °C for 16 h. The mixture was poured into water (50 mL), and the solution was extracted with ethyl acetate (50 mL x 3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by Pre-HPLC (basic) to give compound 310 (14.5 mg, yield: 18 %) as a white solid. MS m/z (ESI): 749.3 [M+H]. [00822] ¹ H NMR (400 MHz, DMSO) δ 8.11 (s, 2H), 7.91 (s, 1H), 7.30 – 7.23 (m, 1H), 7.20 – 7.13 (m, 1H), 5.30 (d, J = 54.4 Hz, 1H), 4.80 – 4.60 (m, 2H), 4.50 – 4.30 (m, 2H), 4.15 – 3.95 (m, 2H), 3.75 – 3.65 (m, 1H), 3.15 – 3.00 (m, 2H), 2.90 – 2.80 (m, 1H), 2.70 – 2.60 (m, 1H), 2.20 – 1.90 (m, 6H), 1.89 – 1.60 (m, 6H), 1.55 – 1.35 (m, 1H), 1.25 – 0.80 (m, 2H), 0.50 – 0.20 (m, 4H). [00823] Example 1f: Synthesis of 333 [00824] Intermediate compound numbering is restricted to the present example.

[00825] Preparation of intermediate 3 [00826] To a solution of intermediate 2 (507 mg, 2.39 mmol) and N,N-Diisopropylethylamine (927 mg, 7.17 mmol) in dry dioxane (5 mL) was added intermediate 1 (600 mg, 2.39 mmol). The reaction was stirred at room temperature for 2 hr. The mixture was poured into ice water (100 mL). The mixture was filtered and the solid was collected to obtain intermediate 3 as a yellow solid. (800 mg, Yield: 78.3 %). MS m/z (ESI): 428.1 [M+H]. [00827] Preparation of intermediate 5 [00828] To a solution of intermediate 3 (400 mg, 0.936 mmol) and DIEA (363 mg, 2.808 mmol) in dioxane (10 ml) was added intermediate 4 (149 mg, 1.872 mmol). The reaction mixture was stirred at 100 ^o C for 12 h. The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel column (DCM/MeOH=20/1) to give intermediate 5 (400 mg, Yield: 77.6 %) as a white solid. MS m/z (ESI): 551.2 [M+H]. [00829] Preparation of intermediate 7 [00830] To a solution of intermediate 5 (900 mg, 1.636 mmol), intermediate 6 (1006 mg, 1.963 mmol) and K ₃ PO ₄ (1042 mg, 4.908 mmol) in dry THF/H ₂ O (16 mL/4 mL) was added cataCXium A Pd G3 (120 mg, 0.164 mmol). The mixture was stirred at 80 ^o C for 3 hr under N ₂ . The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel column (EA: MeOH=20:1) to give intermediate 7 (800 mg, Yield: 54.3 %) as a white solid. MS m/z (ESI): 901.5 [M+H]. [00831] Preparation of intermediate 8 [00832] To a solution of intermediate 7 (200 mg, 0.222 mmol) in dry DMF (5 mL) was added CsF (337 mg, 2.22 mmol). The mixture was stirred at 60 ^o C for 0.5 hr. The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure to give intermediate 8 (150 mg, Yield: 90.7 %) as a white solid. MS m/z (ESI): 745.9 [M+H]. [00833] Preparation of intermediate 9 [00834] To a solution of intermediate 8 (150 mg, 0.2 mmol) in CH ₃ CN (6 mL) was added HCl/dioxane (3 mL, 12 mmol). The solution was stirred at 20 ^o C for 1 h. Then the solution was added dropwise to n-hexane (50 mL), the upper clear liquid was removed and the residue was dissolved in a solution of DCM (100 mL) and MeOH (5 mL). The organic layer was washed by aqueous a.q. NaHCO3, and brine. The organic layer was separated, dried over Na2SO4, concentrated to give intermediate 9 (110 mg, Yield: 90.9 %) as a yellow solid.MS m/z (ESI): 601.2 [M+H]. [00835] Preparation of compound 333 [00836] To a solution of intermediate 9 (80 mg, 0.133 mmol) and DIEA (51 mg, 0.399 mmol) in DMF (2 mL) was added intermediate 10 (21 mg, 0.16 mmol). Then HATU (50 mg, 0.133 mmol) in DMF (1 mL) was added. The mixture was stirred at 30 ^o C for 0.5 h. The mixture was purified by prep-HPLC (basic) to give 333 (3.84 mg, Yield: 4 %) as a white solid. MS m/z (ESI): 710.3 [M+H]. [00837] 1H NMR (400 MHz, DMSO) δ 10.17 (s, 1H), 9.06 (s, 1H), 7.97 (dd, J = 9.2, 6.0 Hz, 1H), 7.60 – 7.33 (m, 2H), 7.18 (d, J = 2.0 Hz, 1H), 5.28 (d, J = 53.6 Hz, 1H), 5.00 – 4.30 (m, 4H), 4.18 – 3.50 (m, 5H), 3.25 – 2.75 (m, 6H), 2.25 – 1.65 (m, 10H), 1.51 – 1.33 (m, 1H), 1.00 – 0.80 (m, 1H), 0.45 – 0.22 (m, 4H). [00838] Example 1g: Synthesis of 357 [00839] Intermediate compound numbering is restricted to the present example. [00840] Synthesis of (4-(7-(2-amino-7-fluorobenzo[d]thiazol-4-yl)-6-chloro-8-fluo ro-2-(((2R,7aS)-2- fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)quinazolin- 4-yl)-6,6-difluoro-1,4-diazepan-1-yl)(3- cyclopropylaziridin-2-yl)methanone (Compound 357)

[00841] To a solution of 2-methylpropane-2-sulfinamide (1-1) (5 g, 41.32 mmol, 1 eq) in dichloromethane (150 mL) at RT, cyclopropanecarbaldehyde (5.78 g, 82.64 mmol, 2 eq) and CuSO ₄ (19.7 g, 123.96 mmol, 3 eq) were added and the resulting solution was stirred at RT overnight. The mixture was filtered, the organic layer was concentrated, and the residue was purified on a silica gel column eluting with ethyl acetate/petroleum (1:10) to afford intermediate 1-2 (6.9 g). ESI-MS m/z: 173.09 [M+H] ⁺ . [00842] To a solution of intermediate 1-2 (2 g, 11.49 mmol, 1 eq) in THF (40 mL) at -78 °C under nitrogen, LiHMDS (23 mL, 22.89 mmol, 2 eq) was added slowly and the resulting solution was stirred at -78 °C for 1 h. To this solution, ethyl 2-bromoacetate (3.84 g, 22.98 mmol, 2 eq) was added and the resulting solution was stirred at - 78 °C for 30 min. Triisopropyl borate (902 mg, 4.8 mmol, 3 eq) was added and then mixture was stirred at RT overnight. The mixture was partitioned between ethyl acetate and NH ₄ Cl aqueous solution. The organic layer was concentrated, and the residue was purified on a silica gel column eluting with ethyl acetate/petroleum (1:12) to afford intermediate 1-3 (2.2g). ESI-MS m/z: 259.12 [M+H] ⁺ . [00843] To a solution of intermediate 1-3 (2.1 g, 8.1 mmol, 1 eq) in THF/H ₂ O (1/1, 20 mL) at RT, LiOH/H ₂ O (1.02 g, 24.3 mmol, 3 eq) was added. The resulting solution was stirred at RT for 2 h. The mixture was neutralized with HCl (1N). The organic layer was concentrated to afford intermediate 1-4 (1.18 g). ESI-MS m/z: 231.09 [M+H] ⁺ . [00844] To a solution of intermediate 1-5 (1 g, 3.05 mmol, 1 eq) in THF (20 mL) at RT, DIEA (1.18 g, 9.15 mmol, 3 eq) and tert-butyl 6,6-difluoro-1,4-diazepane-1-carboxylate (720 mg, 3.05 mmol, 1 eq) were added and the resulting mixture was stirred at 80 °C overnight. The mixture was partitioned between ethyl acetate and water. The organic layer was concentrated and the residue was purified on a silica gel column eluting with ethyl acetate/petroleum (1:4) to afford intermediate 1-6 (1.35 g). ESI-MS m/z: 527.99 [M+H] ⁺ . [00845] To a solution of intermediate 1-6 (1.35 g, 2.56 mmol) in DMSO (15 mL), KF (1.18 g, 20.48 mmol, 8 eq) and ((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methano l (1.22 g, 7.68 mmol, 3 eq) were added and the resulting mixture was stirred at 120 °C under argon for 3 h. The mixture was partitioned between ethyl acetate and water. The organic layer was concentrated. The residue was purified on a silica gel column to afford intermediate 1- 7 (1 g). ESI-MS m/z: 651.12 [M+H]+. [00846] The mixture of intermediate 1-7 (100 mg, 0.153 mmol), (2-((tert-butoxycarbonyl)amino)-7- fluorobenzo[d]thiazol-4-yl)boronic acid (95 mg, 0.306 mmol, 2 eq), K ₃ PO ₄ (97 mg, 0.46 mmol, 3 eq) and 1,1'-Bis (di-t-butylphosphino)ferrocene palladium dichloride (15 mg, 0.023 mmol, 0.15 eq) in dioxane (10 mL) and water (2 mL) was stirred at 100 °C under argon for 3 h. The resulting mixture was diluted with water (20 mL) and extracted with EtOAc (15 mL x 2). The combined organic layer was washed with water and brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by prep-TLC plate to afford intermediate 1-8 (88 mg). ESI-MS m/z: 838.27 [M+H] ⁺ . [00847] To a stirred solution of intermediate 1-8 (88 mg, 0.11 mmol) in DCM (6 mL), trifluoroacetic acid (2 mL) was added and the resulting mixture was stirred at RT for 1 h. The mixture was concentrated in vacuo. The residue was dissolved in DCM and treated with (NH ₃ in MeOH, 7N, 1 mL). The mixture was concentrated to afford intermediate 1-9 (88 mg). ESI-MS m/z: 638.27 [M+H] ⁺ . [00848] To a solution of intermediate 1-4 (34 mg, 0.14 mmol, 1 eq) in DMF (8 mL) at RT, HATU (83 mg, 0.22 mmol, 1.5 eq) was added and the resulting mixture was stirred at RT for 30 min. Intermediate 1-9 (88 mg, 0.14 mmol, 1 eq) and DIEA (56 mg, 0.44 mmol, 3eq) were added. The resulting mixture was stirred at RT for 2 h. The mixture was partitioned between ethyl acetate and H ₂ O. The organic layer was concentrated, and the residue was purified to afford intermediate 1-10 (40 mg). ESI-MS m/z: 852.24 [M+H] ⁺ . [00849] To a solution of intermediate 1-10 (40 mg,0.047 mmol) in MeCN (4 mL), HCl/dioxane (4 mL) was added and the resulting mixture was stirred at RT for 1 h. The mixture was concentrated in vacuo. The residue was dissolved in DCM and treated with (NH ₃ /MeOH, 7 N, 1 mL). The mixture was concentrated, and the residue was purified by prep-TLC plate to afford compound 357 (7 mg). ESI-MS m/z: 750.2 [M+H] ⁺ . [00850] Example 1h: Synthesis of 411 [00851] Intermediate compound numbering is restricted to the present example.

[00852] Preparation of intermediate 2 [00853] To a solution of intermediate 2a (1 g, 0.121 mmol) in CH ₃ CN (5 mL) was added NaOH (320 mg, 0.182 mmol) in H ₂ O (5 mL). The mixture was stirred room temperature for 12 hr. The mixture was concentrated to give intermediate 2 (800 mg, crude) as a white solid. [00854] ¹ H NMR (400 MHz, DMSO) δ 7.50 – 7.40 (m, 6H), 7.30 – 7.20 (m, 9H), 1.79 (d, J = 2.4 Hz, 1H), 1.32 (dd, J = 6.4, 3.2 Hz, 1H), 0.93 (dd, J = 6.4, 2.0 Hz, 1H). [00855] Preparation of intermediate 3 [00856] To a solution of intermediate 1 (100 mg, 0.162 mmol), intermediate 2 (57 mg, 0.162 mmol), and DIEA (63 mg, 0.486 mmol) in DCM (2 mL) was added HATU (62 mg, 0.162 mmol). The mixture was stirred at 25 ^o C for 30 min. The mixture was poured into ice water (50 mL), and the solution was extracted with ethyl acetate (50 mL x 3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel column (DCM/MeOH=20/1) to give intermediate 3 (60 mg, yield: 39.9 %) as a white solid. MS m/z (ESI): 927.4 [M+H]. [00857] Preparation of compound 411 [00858] To a solution of intermediate 3 (60 mg, 0.064 mmol) in CHCl ₃ (1 mL) and MeOH (1 mL) was added TFA (1 mL). The mixture was stirred at 25 ^o C for 1 h. The solvent was removed under reduced pressure. The reaction mixture was diluted with a.q. NaHCO ₃ (20 mL) and DCM (50 mL). The organic layer was concentrated and purified by prep-HPLC to give 411 (7.01 mg, Yield: 15.9 %) as a white solid. MS m/z (ESI): 685.1 [M+H]. [00859] ¹ H NMR (400 MHz, DMSO) δ 7.92 (s, 2H), 7.88 (s, 1H), 7.25 – 7.18 (m, 1H), 7.06 (t, J = 8.8 Hz, 1H), 5.28 (d, J = 54.4 Hz, 1H), 4.80 (s, 1H), 4.66 (s, 1H), 4.39 (d, J = 12.0 Hz, 2H), 4.12 – 4.00 (m, 2H), 3.80 – 3.50 (m, 2H), 3.29 (s, 2H), 3.10 – 3.02 (m, 2H), 3.01 (s, 1H), 2.95 – 2.75 (m, 2H), 2.14 – 1.76 (m, 10H). Example 1i: Synthesis of 2-amino-4-(6-chloro-4-(7-((2R,3S)-3-cyclopropylaziridine-2-c arbonyl)-2,7- diazaspiro[4.5]decan-2-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotet rahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)quinazolin- 7-yl)-7-fluorobenzo[b]thiophene-3-carbonitrile (472).

[00860] Step A: To a solution of compound 1-1 (1 g, 1eq, 3 mmol) and compound 1-2 (720 mg, 1eq, 3 mmol) in i- PrOH (15 ml) was added DIEA (1.16 g, 3eq, 9 mmol). The reaction mixture was stirred at 25 ^o C for 4 h. The mixture was poured into ice water (200 mL). The mixture was filtered and the solid was diluted with MeOH (150 ml). The organic solution was concentrated to dryness under reduced pressure to give compound 1-3 (1 g, Yield: 63%) as a white solid. MS m/z (ESI): 533.0 [M+H] ⁺ . [00861] Step B: To a solution of compound 1-3 (1 g, 1eq, 1.9 mmol) and compound 1-4 (1.5 g, 5eq, 9.5 mmol) in DMSO (10 ml) was added KF (551 mg, 5eq, 9.5 mmol). The reaction mixture was then stirred at 120 ^o C for 16 h. The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The crude was purified by silica gel column chromatography to give compound 1-5 (500 mg, Yield: 40%) as a white solid. MS m/z (ESI): 656.2 [M+H] ⁺ . [00862] Step C: A mixture of compound 1-5 (100 mg, 1eq, 0.15 mmol), compound 1-6 (125 mg, 2 eq, 0.310 mmol), DPEPhosPdCl ₂ (30 mg, 0.27 eq, 0.041 mmol) and Cs ₂ CO ₃ (202 mg, 4 eq, 0.621 mmol) in toluene (8 mL) was stirred at 110 ^o C under N ₂ atmosphere for 3 h. The reaction mixture was filtered, and the filtrate was extracted with EA (50 mL), washed with water (10 mL×3). The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated under reduced pressure to give the residue. The crude product was purified by silica gel column chromatography (MeOH in DCM = 0%~10%) to give compound 1-7 (60 mg, Yield: 46%) as yellow solid. ESI-MS m/z: 868.3 [M+H] ⁺ . [00863] Step D: A solution of compound 1-7 (60 mg, 1eq, 0.07 mmol) in DCM/TFA (6 mL/2 mL) was stirred at 30 oC for 2 h. The reaction solution was alkalized to pH 8 by saturated NaHCO ₃ solution, washed with water, extracted with EtOAc. The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure to give compound 1-8 (40 mg, Yield: 86%) as white solid. ESI-MS m/z: 668.3 [M+H] ⁺ . [00864] Step E: A solution of compound 1-8 (40 mg, 1eq, 0.06 mmol), compound 1-9 (16 mg, 2eq, 0.12 mmol), HOBt (24 mg, 3eq, 0.18 mmol), EDCI (34 mg, 3 eq, 0.18 mmol) and DIEA (31 mg, 4 eq, 0.24 mmol) in DMF (5 mL) was stirred at 30 ^o C for 16 h. The reaction solution was washed with water, extracted with EtOAc. The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated under reduced pressure to give the residue. The crude product was purified by prep-HPLC to give compound 472 (5.26 mg, Yield: 11%) as all white solid. MS m/z (ESI): 777.3 [M+H] ⁺ ; [00865] ¹ H NMR (400 MHz, DMSO-d6) δ 8.25 – 8.0 (m 3H), 7.20 (d, J = 5.2 Hz, 1H), 7.13 (t, J = 8.8 Hz, 1H), 5.27 (d, J = 54.0 Hz, 1H), 4.25 – 3.50 (m, 9H), 3.10 – 3.01 (m, 3H), 2.86 – 2.64 (m, 2H), 2.20 – 1.40 (m, 14H), 1.24 – 0.85 (m, 2H), 0.53 – 0.24 (m, 3H), 0.11 – 0.02 (m, 1H). Example 1j: Synthesis of 2-amino-4-(4-(3-((aziridin-2-ylmethyl)(methyl)amino)-7,8-dih ydro-4H-pyrazolo[1,5- a][1,4]diazepin-5(6H)-yl)-6-chloro-8-fluoro-2-(((2R,7aS)-2-f luorotetrahydro-1H-pyrrolizin-7a(5H)- yl)methoxy)quinazolin-7-yl)-7-fluorobenzo[b]thiophene-3-carb onitrile (320) [00866] Step A: To a solution of 1H-pyrazole-5-carbaldehyde (2-1) (11 g, 114.5 mmol) in MeOH (110 mL) was added 1H-pyrazole-5-carbaldehyde (10.3 g, 137.4 mmol). The mixture was stirred at room temperature under argon for 1 hour. Then the reaction mixture was cooled down to 0 ^o C and added NaBH4 (5.2 g, 137.4 mmol) slowly. The mixture was stirred at 0 ^o C under argon for 1 hour. Then H ₂ O (60 mL) and Boc2O (30 g, 137.4 mmol) were added dropwise at 0 ^o C. The mixture was stirred at room temperature under argon for 3 hours. After completion, the mixture was quenched with NH ₄ Cl (sat.aq, 60 mL), which was extracted with EA (500 mL). The organic layer was dried over Na ₂ SO ₄ and concentrated to dryness. The residue was purified by silica gel column chromatography (DCM: MeOH =20:1) to give compound 2-3 (17 g, yield: 58%) as a yellow oil. MS (ESI) m/z: 256.1 [M+H] ⁺ . [00867] Step B: To a solution of compound 2-3 (15 g, 58.75 mmol) in DCM (150 mL) at 0 ^o C was added TEA (32.7 mL). To the mixture was added methanesulfonyl chloride (9.1 mL) dropwise and stirred at 0 ^o C for 3 hours under argon. After completion, the mixture was quenched with H ₂ O (100 mL), the mixture was extracted with DCM (200 mL). The organic layer was dried over Na ₂ SO ₄ and concentrated to dryness to give compound 2-4 (23.6 g, crude) as a yellow oil. MS (ESI) m/z: 434.0 [M+Na] ⁺ [00868] Step C: To a solution of compound 2-4 (23.6 g, 57.35 mmol) in DMF (200 mL) was added NaH (3.44 g, 86.03 mmol) to 0 ^o C under argon, the mixture was stirred at room temperature for 3 hours. After completion, the mixture was quenched with water (100 mL), extracted with EA (200 mL) and washed with brine (200 mL*2). The organic layer was dried over Na ₂ SO ₄ and concentrated to dryness. The residue was purified by silica gel column chromatography (PE: EA=1:2) to give compound 2-5 (7 g, yield: 51%) as a yellow oil. MS (ESI) m/z: 238.1 [M+H] ⁺ . [00869] Step D: To a solution of compound 2-5 (7 g, 29.5 mmol) in CH ₃ CN (100 mL) was added NIS (7.96 g, 35.4 mmol) and stirred at room temperature for 16 hours under argon. After completion, the reaction mixture was diluted with H ₂ O (100mL) and extracted with EA (100 mL*2). The organic layer was dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by silica gel column (PE: EA= 1:2) to give compound 2-6 (8.9 g, yield: 83.1%) as a yellow solid. MS (ESI) m/z: 364.0 [M+H] ⁺ . [00870] Step E: To a stirred solution of compound 2-6 (5 g, 13.7 mmol) in 1,4-dioxane (30 mL) was added HCl in1,4-dioxane(4M, 30 mL), The reaction mixture was stirred at room temperature for 2 h. After completed, the mixture was concentrated, the crude product (2-7) was used directly for the next step without purification. (6.8 g, yield: 100%). MS (ESI) m/z: 264.1 [M+H] ⁺ . [00871] Step F: To a solution of compound 2-7 (3.62g, 13.7 mmol) in 1,4-dioxane and water (25 mL/25 mL) were added K ₂ CO ₃ (7.4 g, 54 mmol) and CbzCl (3.6 g, 21 mmol) at room temperature under argon. The mixture was stirred at room temperature for 3 h, After completed, the mixture was diluted with EA (100 mL) and washed with brine (50 mL*3). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel column (PE:EA= 1:1) to give compound 2-8 (4.8 g, yield: 88%). MS (ESI) m/z: 398.0 [M+H] ⁺ . [00872] Step G: To a stirred solution of compound 2-8 (1.5 g, 3.8 mmol), CuI (143.4 mg, 0.756 mmol) K3PO4 (1.6 g, 7.56 mmol) 2-((2,6-dimethylphenyl)amino)-2-oxoacetic acid (291 mg, 1.5 mmol) in DMSO (20 mL) was added methanamine (720 mg,22.6 mmol). The reaction mixture was stirred at 120 °C for 2 h. After the completion of the reaction, the mixture was diluted with EA (60 mL) and washed with brine (50 mL*3). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by silica gel column (PE:EA= 4:1) to give the desired product (2-9) as a yellow solid. (700 mg, 61% yield). MS (ESI) m/z: 301.1 [M+H] ⁺ . [00873] Step H: The solution of compound 2-9 (150 mg, 0.5 mmol), 1-tritylaziridine-2-carbaldehyde (313 mg, 1 mmol) in MeOH (8 mL) was stirred for 1 h and then NaCNBH ₃ (37.8 mg, 0.6 mmol) was added. The reaction mixture was stirred at 25 °C for 1 h. After the completion of the reaction, the reaction mixture was poured into water, The mixture was extracted with DCM (40 mL). The organic layer was dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by Prep-TLC (MeOH : DCM=1:15) to give compound 2-10 (170 mg, 57% yield). MS (ESI) m/z: 598.2 [M+H] ⁺ . [00874] Step I: To a solution of compound 2-10 (170 mg, 0.28 mol) in MeOH (8 mL) was added Pd(OH) ₂ /C (10%, 60 mg). The suspension was degassed under vacuum and purged with H ₂ several times. The reaction mixture was stirred at 65°C for 2 h. After the completion of the reaction, the reaction mixture was filtered. The filtrate was concentrated to give crude product. The crude product was purified by Prep-TLC (MeOH:DCM=1:15) to compound 2-11 (65 mg, 49%yield). MS (ESI) m/: 464.3 [M+H] ⁺ . [00875] Step J: To a stirred solution of compound 2-12 (64 mg,0.1 mmol), compound 2-11 (60 mg, 0.129mmol) and DBU (14 mg, 0.09 mmol) in DMF (10 mL) was added PyBOP (48 mg, 0.09 mmol) at room temperature under argon stirred for 2h. After completed, the mixture was diluted with ethyl acetate (60 mL) and washed with brine (50 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by Prep-TLC (MeOH:DCM=1:15) to give compound 2-13 (38 mg, 26% yield). MS (ESI) m/z: 1091.3 [M+H] ⁺ . [00876] Step K: To a stirred solution of compound 2-13 (38 mg, 0.034 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 ml) at room temperature under argon and then stirred for 2h. After completed, NH ₃ in MeOH(7N) solution was added to adjust the pH to 8. The reaction mixture was concentrated and the residue was purified by Prep-TLC (NH ₃ in MeOH (7N):DCM=1:10) to give compound 320 (3.86 mg, 14% yield). MS (ESI) m/z: 749.6 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 2H), 7.92 (s, 1H), 7.28 (d, J = 18.2 Hz, 1H), 7.28 – 7.17 (m, 1H), 7.14 (t, J = 8.9 Hz, 1H), 5.27 (d, J = 54.0 Hz, 1H), 5.09 – 4.86 (m, 2H), 4.36 (s, 2H), 4.06 (dd, J = 36.1, 10.3 Hz, 4H), 3.07 (t, J = 12.4 Hz, 2H), 3.01 (s, 1H), 2.82 (d, J = 6.5 Hz, 1H), 2.74 – 2.58 (m, 5H), 2.36 – 2.18 (m, 2H), 2.18 – 2.09 (m, 1H), 2.03 (d, J = 16.6 Hz, 3H), 1.79 (dd, J = 32.4, 13.2 Hz, 3H), 1.53 (s, 1H). Example 1k: Synthesis of 2-amino-4-(6-chloro-4-(4-((2R,3S)-3-cyclopropylaziridine-2- carbonyl)hexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl)-8-fluoro-2- (((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)- yl)methoxy)quinazolin-7-yl)-7-fluorobenzo[b]thiophene-3-carb onitrile (405). [00877] Step A: To a solution of compound 1-1 (1 g, 1eq, 3 mmol) and compound 3-1 (636 mg, 1 eq, 3 mmol) in i- PrOH (15 ml) was added DIEA (1.16 g, 3eq, 9 mmol). The reaction mixture was stirred at 25 ^o C for 4 h. The mixture was poured into ice water (200 mL). The mixture was filtered and the solid was diluted with MeOH (150 ml). The organic solution was concentrated to dryness under reduced pressure to give compound 3-2 (1.1 g, Yield: 73%) as a white solid. MS m/z (ESI): 505.0 [M+H] ⁺ . [00878] Step B: To a solution of compound 3-2 (1 g, 1eq, 2 mmol) and compound 1-4 (1.5 g, 5eq, 10 mmol) in DMSO (10 ml) was added KF (580 mg, 5eq, 10 mmol). The reaction mixture was then stirred at 120 ^o C for 16 h. The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The crude was purified by silica gel column chromatography to give compound 3-3 (500 mg, Yield: 40 %) as a white solid. MS m/z (ESI): 628.1 [M+H] ⁺ . [00879] Step C: A mixture of compound 3-3 (130 mg, 1eq, 0.207 mmol), compound 1-6 (125 mg, 1.5 eq, 0.31 mmol), DPEPhosPdCl ₂ (30 mg, 0.2 eq, 0.041 mmol) and Cs ₂ CO ₃ (202 mg, 3 eq, 0.62 mmol) in toluene (8 mL) was stirred at 110 ^o C under N ₂ atmosphere for 3 h. The reaction mixture was filtered, and the filtrate was extracted with EA (50 mL), washed with water (10 mL×3). The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure. The crude product was purified by silica gel column chromatography (MeOH in DCM = 0%~10%) to give compound 3-4 (140 mg, Yield: 80%) as yellow solid. ESI-MS m/z: 840.3 [M+H] ⁺ . [00880] Step D: A solution of compound 3-4 (140 mg, 1eq, 0.16 mmol) in DCM/TFA (6 mL/2 mL) was stirred at 30 ^o C for 2 h. The reaction solution was alkalized to pH 8 by saturated NaHCO ₃ solution, washed with water, extracted with EtOAc. The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure to give compound 3-5 (60 mg, Yield: 56%) as white solid. ESI-MS m/z: 640.2 [M+H] ⁺ . [00881] Step E: A solution of compound 3-5 (60 mg, 1 eq, 0.094 mmol), compound 1-9 (37 mg, 3 eq, 0.28 mmol), HOBt (38 mg, 3 eq, 0.28 mmol), EDCI (54 mg, 3eq, 0.281 mmol) and DIEA (36 mg, 3eq, 0.281 mmol) in DMF (5 mL) was stirred at 30 ^o C for 16 h. The reaction solution was washed with water, extracted with EtOAc. The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure. The crude product was purified by prep-HPLC to give compound 405 (P1: 5.84 mg, P2: 5.06 mg, Yield: 15%) as all white solid.405 (P2): MS m/z (ESI): 749.6 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 8.12 (d, J = 8.8 Hz, 3H), 7.24 – 7.15 (m, 2H), 5.40 – 5.10 (m, 2H), 5.00 – 4.50 (m, 1H), 4.25 – 3.75 (m, 6H), 3.20 – 3.00 (m, 3H), 2.83 (s, 1H), 2.36 – 2.23 (m, 3H), 2.18 – 1.98 (m, 6H), 1.90 – 1.75 (m, 3H), 1.46 – 1.33 (m, 1H), 0.96 – 0.80 (m, 1H), 0.44 – 0.24 (m, 4H). Example 1l: Synthesis of 2-amino-4-(6-chloro-4-(2-((2R,3S)-3-cyclopropylaziridine-2-c arbonyl)-6-oxa-2,9- diazaspiro[3.6]decan-9-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotet rahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)quinazolin- 7-yl)-7-fluorobenzo[b]thiophene-3-carbonitrile (352) [00882] Step A: The mixture of compound 2-12 (80 mg, 1 eq., 0.12 mmol), compound 4-1 (90 mg, 3 eq., 0.37 mmol), PyBOP (193 mg, 3 eq., 0.37 mmol) and DIEA (48 mg, 3 eq., 0.37 mmol) in DMF (6 mL) was stirred at room temperature for 2 h. The reaction solution was extracted with EtOAc (50 mL), washed with water (10 mL×3). The combined organic layer was washed with brine, dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography to obtain 4-2 (70 mg, Yield: 64%). ESI-MS m/z: 870.3 [M+H] ⁺ . [00883] Step B: A solution of compound 4-2 (70 mg, 1 eq., 0.080 mmol) in DCM/TFA (4 mL/1 mL) was stirred at room temperature for 2 h. The reaction solution was alkalized to pH 8 by saturated NaHCO ₃ solution, washed with water, and extracted with EA. The crude product was purified by reverse phase column (MeOH in H ₂ O (0.2% NH ₃ .H ₂ O) = 0%~100%) to give compound 4-3 (40 mg, Yield: 74%) as white solid. ESI-MS m/z: 670.1 [M+H] ⁺ . [00884] Step C: The mixture of compound 4-3 (40 mg, 1 eq., 0.060 mmol), compound 1-9 (24 mg, 3 eq., 0.180 mmol), HOBt (24 mg, 3 eq., 0.180 mmol), EDCI (34 mg, 3 eq., 0.180 mmol) and DIEA (23 mg, 3 eq., 0.180 mmol) in DMF (5 mL) was stirred at RT for 16 h. The reaction solution was washed with water, and extracted with EA. The crude product was purified by prep-HPLC to give compound 352 (2.41 mg) as white solid. ESI-MS m/z: 779.6 [M+H] ⁺ .1H NMR (400 MHz, DMSO-d ₆ ) δ 8.15 – 8.00 (m, 3H), 7.24 (dd, J = 8.4, 5.2 Hz, 1H), 7.15 (t, J = 8.8 Hz, 1H), 5.27 (d, 1H), 4.50 – 3.60 (m, 13H), 3.20 – 3.00 (m, 3H), 2.82 (d, J = 6.6 Hz, 1H), 2.12 (d, J = 10.8 Hz, 2H), 2.03 (d, J = 14.8 Hz, 3H), 1.89 – 1.71 (m, 4H), 1.31 – 1.09 (m, 2H), 0.87 (s, 1H), 0.50 – 0.20 (m, 4H). Example 1m: Synthesis of 2-amino-4-(4-((1R,5S)-8-(aziridin-2-ylmethyl)-3,8-diazabicyc lo[3.2.1]octan-3-yl)-6- chloro-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizi n-7a(5H)-yl)methoxy)quinazolin-7-yl)-7- fluorobenzo[b]thiophene-3-carbonitrile (336).

[00885] Step A: To a solution of compound 2-12 (300 mg, 0.45 mmol) in DMF (10 mL) were added compound 5-1 (116 mg, 0.54 mmol), PyBop (712 mg, 1.36 mmol) and DBU (208 mg, 1.36 mmol). The mixture was stirred at room temperature for 1 h under argon. The mixture was extracted with EA (20 mL) and washed with brine (20 mL*2). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography (MeOH: DCM=1:10) to give compound 5-2 (550 mg, 100% yield). ESI-MS m/z: 840.3 [M+H] ⁺ . [00886] Step B: To a solution of compound 5-2 (500 mg, 0.6 mmol) in DCM (10 mL) was added TFA (3 mL). The mixture was stirred at room temperature for 1 h. The mixture was alkalized with 7N NH ₃ -MeOH. The mixture was concentrated in vacuo and purified by prep-TLC (NH ₃ -MeOH (7N): DCM =1:10) to give compound 5-3 (200 mg, 52% yield). ESI-MS m/z: 641.7 [M+H] ⁺ . [00887] Step C A solution of compound 5-3 (50 mg, 0.078 mmol) and compound 5-4 (27 mg, 0.086 mmol) in MeOH (5 mL) was stirred at room temperature for 1 h. Then NaCNBH ₃ (6 mg, 0.095 mmol) and a drop of AcOH were added. The mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by prep-TLC (MeOH:DCM=1:10) to give compound 5-5 (30 mg, 41% yield). ESI-MS m/z: 937.2 [M+H] ⁺ . [00888] Step D: To a solution of compound 5-5 (30 mg, 0.032 mmol) in DCM (2 mL) was added TFA (1 mL). The mixture was stirred at room temperature for 1 h. The mixture was alkalized with 7N NH ₃ in MeOH and concentrated in vacuo. The crude product was purified by Prep-TLC (NH ₃ in MeOH(7N) : DCM =1:10) to give compound 336 (6.31 mg, 27% yield). ESI-MS m/z: 695.2 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 2H), 7.87 (s, 1H), 7.26 (dd, J = 8.2, 5.3 Hz, 1H), 7.18 – 7.11 (m, 1H), 5.27 (d, 1H), 4.26 (dd, J = 25.2, 11.6 Hz, 2H), 4.08 (d, J = 10.1 Hz, 1H), 3.99 (d, J = 10.4 Hz, 1H), 3.62 (dd, J = 28.7, 12.2 Hz, 2H), 3.51 (s, 1H), 3.40 (s, 1H), 3.14 – 2.96 (m, 3H), 2.82 (d, J = 6.2 Hz, 1H), 2.50-1.50 (m, 10H). Example 1n: Synthesis of 2-amino-4-(6-chloro-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro -1H-pyrrolizin-7a(5H)- yl)methoxy)-4-((1R,5S)-8-((R)-1-(methylsulfonyl)aziridine-2- carbonyl)-3,8-diazabicyclo[3.2.1]octan-3- yl)quinazolin-7-yl)-7-fluorobenzo[b]thiophene-3-carbonitrile (347).

[00889] Step A: To a solution of compound 5-3 (80 mg, 1eq, 0.12 mmol), compound 6-1 (88 mg, 2 eq, 0.25 mmol) and DIEA (48 mg, 3 eq, 0.37 mmol) in dry DMF (3 mL) was added T3P (60 mg, 1.5 eq, 0.187 mmol) in dry DMF (1 mL) at 0 ℃ under N ₂ . The mixture was stirred at room temperature for 3 h under N ₂ . The mixture was poured into ice water (100 mL), and the solution was extracted with ethyl acetate (50 mL x 3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by Prep-TLC (DCM: MeOH=10:1) to give compound 6-2 (50 mg, Yield: 42%) as a yellow solid. MS m/z (ESI): 851.3 [M+H] ⁺ . [00890] Step B: To a solution of compound 6-2 (50 mg, 1 eq, 0.053 mmol) in dry DCM/MeOH (3/3 mL) was added TFA (3 mL). The mixture was stirred at 0 ℃ for 3 h. The solvent was removed under reduced pressure. The reaction mixture was diluted with a.q. NaHCO ₃ (10 mL) and EA (50 mL), and the solution was extracted with ethyl acetate (50 mL x 3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure to give compound 6-3 (35 mg, Yield: 94%) as yellow solid. MS m/z (ESI): 709.2 [M+H] ⁺ . [00891] Step C: To a solution of compound 6-4 (35 mg, 1 eq, 0.049 mmol), DMAP (9 mg, 1.5 eq, 0.074 mmol) and TEA (7.5 mg, 0.1.5 eq, 074 mmol) in dry DCM (2 mL) was added compound 6-3 (8.5 mg, 1.5 eq, 0.074 mmol) in dry DCM (1 mL). The mixture was stirred at room temperature for 3 h. The mixture was poured into water (50 mL), and the solution was extracted with ethyl acetate (50 mL x 3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by prep-HPLC to give compound 347 (4.1 mg, Yield: 11%) as white solid. MS m/z (ESI): 787.4 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 8.07 (s, 2H), 7.86 (s, 1H), 7.22 (s, 1H), 7.11 (t, J = 9.2 Hz, 1H), 5.27 (d, J = 52.8 Hz, 1H), 4.80 – 4.60 (m, 2H), 4.55 – 4.25 (m, 2H), 4.20 – 3.95 (m, 2H), 3.78 – 3.43 (m, 3H), 3.25 (s, 3H), 3.10 – 3.00 (m, 3H), 2.82 (d, J = 6.4 Hz, 1H), 2.68 – 2.62 (m, 2H), 2.15 – 2.00 (m, 4H), 1.95 - 1.70 (m, 5H). Example 1o: Synthesis of 2-amino-4-((R)-6-chloro-4-((2S,5R)-4-((2R,3S)-3-cyclopropyla ziridine-2-carbonyl)-2,5- dimethylpiperazin-1-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrah ydro-1H-pyrrolizin-7a(5H)-yl)methoxy)quinazolin-7- yl)-7-fluorobenzo[b]thiophene-3-carbonitrile (302A).

[00892] Step A: A solution of compound 7-1 (70 mg, 1eq, 0.11 mmol), compound 7-2 (69 mg, 3eq, 0.32 mmol ), PyBOP (169 mg, 3eq, 0.32 mmol) and DIEA (42 mg, 3eq, 0.32 mmol) in DMF (6 mL) was stirred at 30 ^o C for 2 h. The reaction solution was extracted with EtOAc (50 mL), washed with water (10 mL×3). The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure. The crude product was purified by silica gel column chromatography (MeOH in DCM = 0%~10%) to give compound 7-3 (75 mg, Yield: 82%) as yellow solid. MS m/z (ESI): 842.2 [M+H] ⁺ . [00893] Step B: A solution of compound 7-3 (75 mg, 1eq, 0.089 mmol) in DCM/TFA (4 mL/1 mL) was stirred at 30 ^o C for 2 h. The reaction solution was alkalized to pH 8 by saturated NaHCO ₃ solution, washed with water, extracted with EtOAc. The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure to give compound 7-4 (42 mg, Yield: 73%) as white solid. MS m/z (ESI): 642.1 [M+H] ⁺ . [00894] Step C: A solution of compound 7-4 (42 mg, 1eq, 0.065 mmol), compound 1-9 (26 mg, 3eq, 0.19 mmol), HOBt (26 mg, 3eq, 0.19 mmol), EDCI (38 mg, 3eq, 0.19 mmol) and DIEA (25 mg, 3eq, 0.196 mmol) in DMF (5 mL) was stirred at 30 ^o C for 16 h. The reaction solution was washed with water, extracted with EA. The crude product was purified by prep-HPLC to give 302A (27.4 mg, Yield: 56%) as white solid. MS m/z (ESI): 751.5 [M+H] ⁺ .1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 2H), 7.88 (s, 1H), 7.30 – 7.25 (m, 1H), 7.16 (t, J = 8.8 Hz, 1H), 5.28 (d, J = 54.0 Hz, 1H), 4.90 – 4.60 (m, 2H), 4.17 – 3.79 (m, 6H), 3.48 (dd, J = 13.6, 3.2 Hz, 1H), 3.10 (t, J = 10.8 Hz, 2H), 3.02 (d, J = 11.2 Hz, 1H), 2.84 – 2.75 (m, 1H), 2.56 (dd, J = 7.2, 2.4 Hz, 1H), 2.20 – 1.91 (m, 4H), 1.89 – 1.76 (m, 3H), 1.48 (dd, J = 15.2, 7.2 Hz, 1H), 1.32 – 1.25 (m, 3H), 1.16 (d, J = 6.4 Hz, 1H), 1.07 (d, J = 6.8 Hz, 1H), 0.94 – 0.83 (m, 1H), 0.47 – 0.22 (m, 4H). Example 1p: Synthesis of 2-amino-4-(6-chloro-4-(9-((2R,3S)-3-cyclopropylaziridine-2-c arbonyl)-3,9- diazabicyclo[4.2.1]nonan-3-yl)-8-fluoro-2-(((2R,7aS)-2-fluor otetrahydro-1H-pyrrolizin-7a(5H)- yl)methoxy)quinazolin-7-yl)-7-fluorobenzo[b]thiophene-3-carb onitrile (398).

[00895] Step A: A solution of compound 2-12 (80 mg, 1eq, 0.12 mmol), compound 8-1 (56 mg, 2eq, 0.24 mmol), PyBOP (129 mg, 2eq, 0.24 mmol) and DIEA (64 mg, 4eq, 0.4 mmol) in DMF (6 mL) was stirred at 30 ^o C for 2 h. The reaction solution was extracted with EtOAc (50 mL), washed with water (10 mL×3). The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure. The crude product was purified by silica gel column chromatography (MeOH in DCM = 0%~10%) to give compound 8-2 (75 mg, Yield: 71%) as yellow solid.MS m/z (ESI): 854.3 [M+H] ⁺ . [00896] Step B: A solution of compound 8-2 (75 mg, 1eq, 0.089 mmol) in DCM/TFA (4 mL/1 mL) was stirred at 30 ^o C for 2 h. The reaction solution was alkalized to pH 8 by saturated NaHCO ₃ solution, washed with water, extracted with EtOAc. The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure to give compound 8-3 (40 mg, Yield: 69%) as white solid. MS m/z (ESI): 654.3 [M+H] ⁺ . [00897] Step C: A solution of compound 8-3 (40 mg, 1eq, 0.061 mmol), compound 1-9 (26 mg, 3.2 eq, 0.19 mmol), HOBt (26 mg, 3.2 eq, 0.19 mmol), EDCI (38 mg, 3.2 eq, 0.19 mmol) and DIEA (25 mg, 3.2 eq, 0.19 mmol) in DMF (5 mL) was stirred at 30 ^o C for 16 h. The reaction solution was washed with water, extracted with EtOAc. The crude product was purified by prep-HPLC to give 398 (1.7 mg, Yield: 4%) as white solid. MS m/z (ESI): 763.2 [M+H] ⁺ ; ¹ H NMR (400 MHz, CDCl3) δ 7.90 – 7.25 (m, 1H), 7.24 – 7.18 (m, 1H), 7.07 – 6.99 (m, 1H), 5.50 – 5.20 (m, 2H), 4.89 – 4.59 (m, 2H), 4.44 – 3.78 (m, 4H), 3.50 – 3.05 (m, 4H), 2.98 (s, 1H), 2.49 – 1.99 (m, 10H), 1.98 – 1.80 (m, 5H), 0.88 (s, 1H), 0.60 – 0.25 (m, , 4H). Example 1q: Synthesis of (2R,3S)-N-((3R)-1-(7-(2-amino-3-cyano-7-fluorobenzo[b]thioph en-4-yl)-6-chloro-8- fluoro-2-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)- yl)methoxy)quinazolin-4-yl)pyrrolidin-3-yl)-3- cyclopropyl-N-methylaziridine-2-carboxamide (303D).

[00898] Step A: To a solution of compound 2-12 (80 mg, 1 eq., 0.12 mmol), compound 9-1 (74 mg, 3 eq., 0.37 mmol), PyBOP (193 mg, 3 eq., 0.37 mmol) and DIEA (48 mg, 3 eq., 0.37 mmol) in DMF (6 mL) was stirred at room temperature for 2 h. The reaction solution was extracted with EA (50 mL), washed with water (10 mL×3). The combined organic layers were washed with brine, dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography to give compound 9-2 (65 mg, Yield: 63%). ESI-MS m/z (ESI): 828.1 [M+H] ⁺ . [00899] Step B: To a solution of compound 9-2 (65 mg, 1 eq., 0.078 mmol) in DCM/TFA (4 mL/1 mL) was stirred at room temperature for 2 h. The reaction solution was alkalized to pH 8 by saturated NaHCO ₃ solution, washed with water, extracted with EA. The crude product was purified by reverse phase column (MeOH in H ₂ O (0.2% NH ₃ .H ₂ O) = 0%~100%) to give compound 9-3 (43 mg, Yield: 87%) as white solid. ESI-MS m/z (ESI): 628.5 [M+H] ⁺ . [00900] Step C: To a solution of compound 9-3 (43 mg, 1 eq., 0.068 mmol), compound 1-9 (27 mg, 3 eq., 0.20 mmol), HOBt (27 mg, 3 eq., 0.20 mmol), EDCI (39 mg, 3 eq., 0.20 mmol) and DIEA (26 mg, 3 eq., 0.20 mmol) in DMF (5 mL) was stirred at RT for 16 h. The reaction solution was washed with water, extracted with EA. The crude product was purified by prep-HPLC to give compound 303D (4.2 mg) as white solid. ESI-MS m/z (ESI): 737.2 [M+H] ⁺ ; [00901] ¹ H NMR (400 MHz, DMSO-d6) δ 8.25 – 8.0 (m, 3H), 7.27 – 7.18 (m, 1H), 7.15 (t, J = 8.8 Hz, 1H), 5.27 (d, J = 53.8 Hz, 1H), 5.20 – 4.90 (m, 1H), 4.20 – 3.80 (m, 6H), 3.20 – 2.75 (m, 5H), 2.30 - 1.75 (m, 11H), 1.50 – 1.37 (m, 1H), 1.20 – 0.90 (s, 2H), 0.49 – 0.23 (m, 4H). Example 1r: Synthesis of 4-(4-((1R,5S)-8-((2R,3R)-1-acetyl-3-cyclopropylaziridine-2-c arbonyl)-3,8- diazabicyclo[3.2.1]octan-3-yl)-6-chloro-8-fluoro-2-(((2R,7aS )-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)- yl)methoxy)quinazolin-7-yl)-2-amino-7-fluorobenzo[b]thiophen e-3-carbonitrile (331).

[00902] Step A: A solution of compound 5-3 (300 mg, 1 eq, 0.469 mmol), compound 10-1 (217 mg, 2 eq, 0.937 mmol), HOBT (190 mg, 3 eq, 1.41 mmol), EDCI (270 mg, 3 eq, 1.41 mmol) and DIEA (182 mg, 3 eq, 1.41 mmol) in DMF (8 mL) was stirred at 30 ^o C for 16 h. The reaction solution was extracted with EtOAc (50 mL), washed with water (10 mL×3). The organic phase was dried by anhydrous Na ₂ SO ₄ , concentrated to give the residue under reduced pressure. The crude product was purified by silica gel column (MeOH in DCM = 0%~10%) to give compound 10-2 (240 mg, Yield: 60%) as yellow solid. MS m/z (ESI): 853.2 [M+H] ⁺ . [00903] Step B: A solution of compound 10-2 (240 mg, 1 eq, 0.28 mmol) in THF (10 mL) was cooled to 0 ^o C with ice water. HI (72 mg, 2 eq, 0.56 mmol) was added dropwise under stirring at 0 ^o C. The solution was stirred at 0 ^o C for 2 h. The reaction solution was alkalized to pH 8 by Ammonium hydroxide and concentrated to give residue. The crude product was purified by reverse column (MeCN in H ₂ O (0.2% NH ₃ .H ₂ O) = 0%~100%) to give compound 10- 3 (130 mg, Yield: 61%) as white solid. MS m/z (ESI): 749.1 [M+H] ⁺ . [00904] Step C: To a solution of compound 10-3 (55 mg, 1 eq, 0.073 mmol), CH ₃ COOH (5.3 mg, 1.2 eq, 0.088 mmol), and DIEA (29 mg, 3 eq, 0.22 mmol) in DMF (2 mL) was added HATU (31 mg, 1.1 eq, 0.08 mmol) at 0 ^o C and stirred at this temperature for 20 min. The mixture was poured into water (50 mL), and the solution was extracted with ethyl acetate (50 mL x 3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by prep-HPLC to give 331 (0.9 mg) as white solid. MS m/z (ESI): 791.6 [M+H] ⁺ ; 1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 2H), 7.89 (s, 1H), 7.26 (s, 1H), 7.15 (t, J = 8.8 Hz, 1H), 5.21 (d, 1H), 4.97 – 4.26 (m, 8H), 4.15 – 3.90 (m, 3H), 3.12 – 2.99 (m, 3H), 2.82 (s, 1H), 2.18 (s, 1H), 2.06 – 1.90 (m, 6H), 1.77 – 1.50 (m, 5H), 0.85 – 0.70 (m, 1H), 0.70 – 0.20 (m, 4H). Table 1

“A” indicates the compound is a single atropisomer and if another single atropisomer of the compound is present in the table, then each atropisomer is a different atropisomer; “D” indicates the compound is a single diastereomer and if additional single diastereomer of the compound are present in the table, then each diastereomer is a different diastereomer. Compounds may be present as all possible atropisomers, isomers, and/or diastereomers unless the structure of Table 1, compound name of Table 1, or the note described above (e.g., A, D) indicates the compound is a specific atropisomer, isomer, diastereomer, or specific mixture thereof. EXAMPLE 2: Ras sequences Human K-Ras Wildtype sequence (SEQ ID NO.1) 1 MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI 101 KRVKDSEDVP MVLVGNKCDL PSRTVDTKQA QDLARSYGIP FIETSAKTRQ 151 GVDDAFYTLV REIRKHKEKM SKDGKKKKKK SKTKCVIM Human K-Ras G12D (SEQ ID NO.2) 1 MTEYKLVVVG ADGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI 101 KRVKDSEDVP MVLVGNKCDL PSRTVDTKQA QDLARSYGIP FIETSAKTRQ 151 GVDDAFYTLV REIRKHKEKM SKDGKKKKKK SKTKCVIM Human K-Ras G12V (SEQ ID NO.3) 1 MTEYKLVVVG AVGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI 101 KRVKDSEDVP MVLVGNKCDL PSRTVDTKQA QDLARSYGIP FIETSAKTRQ 151 GVDDAFYTLV REIRKHKEKM SKDGKKKKKK SKTKCVIM Human K-RasG12S (SEQ ID NO.4): 1 MTEYKLVVVG ASGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI 101 KRVKDSEDVP MVLVGNKCDL PSRTVDTKQA QDLARSYGIP FIETSAKTRQ 151 GVDDAFYTLV REIRKHKEKM SKDGKKKKKK SKTKCVIM Human N-Ras wildtype (SEQ ID NO.5) 1 MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNSKSF ADINLYREQI 101 KRVKDSDDVP MVLVGNKCDL PTRTVDTKQA HELAKSYGIP FIETSAKTRQ 151 GVEDAFYTLV REIRQYRMKK LNSSDDGTQG CMGLPCVVM H-Ras G12D (SEQ ID NO.6) 1 MTEYKLVVVG ADGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI 101 KRVKDSDDVP MVLVGNKCDL AARTVESRQA QDLARSYGIP YIETSAKTRQ 151 GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS H-Ras wildtype (SEQ ID NO.7) 1 MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI 101 KRVKDSDDVP MVLVGNKCDL AARTVESRQA QDLARSYGIP YIETSAKTRQ 151 GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS Human N-Ras G12D (SEQ ID NO.8) 1 MTEYKLVVVG ADGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 51 CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNSKSF ADINLYREQI 101 KRVKDSDDVP MVLVGNKCDL PTRTVDTKQA HELAKSYGIP FIETSAKTRQ 151 GVEDAFYTLV REIRQYRMKK LNSSDDGTQG CMGLPCVVM EXAMPLE 3: Protein expression [00905] DNA expression constructs encoding one or more protein sequences of interest (e.g., Kras fragments thereof, mutant variants thereof, etc.) and its corresponding DNA sequences are optimized for expression in E. coli and synthesized by, for example, the GeneArt Technology at Life Technologies. In some cases, the protein sequences of interest are fused with a tag (e.g., glutathione S-transferase (GST), histidine (His), or any other affinity tags) to facilitate recombinant expression and purification of the protein of interest. Such tag can be cleaved subsequent to purification. Alternatively, such tag may remain intact to the protein of interest and may not interfere with activities (e.g., target binding and/or phosphorylation) of the protein of interest [00906] A resulting expression construct is additionally encoded with (i) att-site sequences at the 5’and 3’ ends for subcloning into various destination vectors using, for example, the Gateway Technology, as well as (ii) a Tobacco Etch Virus (TEV) protease site for proteolytic cleavage of one or more tag sequences. The applied destination vectors can be a pET vector series from Novagen (e.g., with ampicillin resistance gene), which provides an N- terminal fusion of a GST-tag to the integrated gene of interest and/or a pET vector series (e.g., with ampicillin resistance gene), which provides a N-terminal fusion of a HIS-tag to the integrated gene. To generate the final expression vectors, the expression construct of the protein of interest is cloned into any of the applied destination ventors. The expression vectors are transformed into E. coli strain, e.g., BL21 (DE3). Cultivation of the transformed strains for expression is performed in 10 L and 1 L fermenter. The cultures are grown, for example, in Terrific Broth media (MP Biomedicals, Kat. #113045032) with 200 ug/mL ampicillin at a temperature of 37 ºC to a density of 0.6 (OD600), shifted to a temperature of ~27 ºC (for K-Ras expression vectors) induced for expression with 100 mM IPTG, and further cultivated for 24 hours. After cultivation, the transformed E. coli cells are harvested by centrifugation and the resulting pellet is suspended in a lysis buffer, as provided below, and lysed by passing three-times through a high pressure device. The lysate is centrifuged (49000g, 45 min, 4 ºC) and the supernatant is used for further purification. EXAMPLE 4: Ras protein purification [00907] A Ras (e.g., K-Ras wildtype or a mutant such as K-Ras G12S, K-Ras G12D, K-Ras G12V or K-RasG12C) construct or a variant thereof is tagged with GST. E. coli culture from a 10L fermenter is lysed in lysis buffer (50mM Tris HCI 7.5, 500mM NaCI,1 mM DTT, 0,5% CHAPS, Complete Protease Inhibitor Cocktail-(Roche)). As a first chromatography step, the centrifuged lysate is incubated with 50mL Glutathione Agarose 4B (Macherey- Nagel; 745500.100) in a spinner flask (16 h, 10Ό). The Glutathione Agarose 4B loaded with protein is transferred to a chromatography column connected to a chromatography system, e.g., an Akta chromatography system. The column is washed with wash buffer (50mM Tris HCI 7.5, 500mM NaCI, 1 mM DTT) and the bound protein is eluted with elution buffer (50mM Tris HCI 7.5, 500mM NaCI, 1 mM DTT, 15mM Glutathione). The main fractions of the elution peak (monitored by OD280) are pooled. For further purification by size-exclusion chromatography, the above eluate volume is applied to a column Superdex 200 HR prep grade (GE Healthcare) and the resulting peak fractions of the eluted fusion protein is collected. Native mass spectrometry analyses of the final purified protein construct can be performed to assess its homogeneous load with GDP. EXAMPLE 5: HTRF (homogenous time-resolved fluorescence resonance energy transfer assay [00908] The ability of a compound of the present disclosure to reduce a Ras signaling output can be demonstrated by an HTRF assay. This assay can be also used to assess a selective inhibition or reduction of signaling output of a mutant Ras protein relative to a wildtype, or relative to a different mutant Ras protein. For example, the equilibrium interaction of wildtype Kras or K-Ras mutant (e.g., wildtype or a mutant thereof) with SOS1 (e.g., hSOS1) can be assessed as a proxy or an indication for a subject compound’s ability to bind and inhibit Ras protein. HTRF assay detects from (i) a fluorescence resonance energy transfer (FRET) donor (e.g., antiGST- Europium) that is bound to GST-tagged K-Ras mutant to (ii) a FRET acceptor (e.g., anti-6His-XL665) bound to a His-tagged hSOS1. [00909] The assay buffer can contain ~5 mM HEPES pH 7.4, ~150 mM NaCI, ~ 1 mM DTT, 0.05% BSA and 0.0025% (v/v) Igepal. A Ras working solution is prepared in an assay buffer containing typically a suitable amount of the protein construct (e.g., GST-tagged K-Ras mutant) and the FRET donor (e.g., antiGST- Eu(K) from Cisbio, France). A SOS1 working solution is prepared in an assay buffer containing suitable amount of the protein construct (e.g., His-hSOS1) and the FRET acceptor (e.g., anti-6His-XL665 from Cisbio, France). A suitable amount of the protein construct will depend on the range of activity or range of IC50 values being detected or under investigation. For detecting IC50 within a range of 500 nM, the protein constructs of the same range of molarity can be utilized. An inhibitor control solution is prepared in an assay buffer containing comparable amount of the FRET acceptor without the SOS1 protein. [00910] A fixed volume of DMSO with or without test compound is transferred into a 384-well plate. Ras working solution is added to all wells of the test plate. SOS1 working solution is added to all wells except for those that are subsequently filled the inhibitor control solution. Upon incubation for about 10 minutes or longer, the fluorescence is measured with a M1000Pro plate reader (Tecan) using HTRF detection (excitation 337nm, emission 1 : 620nm, emission 2: 665nm). Compounds are tested in duplicates at different concentrations (for example, 10 μΜ, 2.5 μΜ, 0.63 μΜ, 0.16 μΜ, 0.04 μΜ, 0.01 μΜ test compound). The ratiometric data (i.e., emission 2 divided by emission 1) is used to calculate IC50 values against Ras using GraphPad Prism (GraphPad software). Following this general procedure, samples are tested with or without a subject compound disclosed herein to assess their abilities to inhibit a K-Ras mutant relative to another mutant or WT. Signaling output measured in terms of IC50 values can be obtained, a ratio of IC50 against one mutant relative to another mutant can be calculated. For instance, a selective reduction of K-Ras G12D signaling output can be evidenced by a ratio greater than one. In particular, a selective reduction of K-Ras G12D signaling relative to K-Ras WT signaling is evidenced as the ratio of IC50 (against K-Ras WT) to IC50 (against K-Ras G12D) is greater than 1. [00911] Table 2 ++ IC50 greater than or equal to 5 µM; +++ IC50 less than 5 µM; ND is not determined EXAMPLE 6: GTPase activity assay [00912] The ability of any compound of the present disclosure to inhibit a Ras protein signalling can be demonstrated by a reduced GTPase activity. This assay can be also used to assess a selective inhibition of a mutant Ras protein relative to a wildtype, or relative to a different mutant Ras protein. For instance, the assay can be used to establish a subject compound’s ability to selectively inhibit Kras G12D relative to wildtype, G12S relative to wildtype, Kras G12V relative to wildtype, KrasG12S relative KrasG12V, KrasG12S relative KrasG12D, KrasG12D relative KrasG12S, or KrasG12D relative KrasG12V. In particular, intrinsic and GTPase-activating protein (GAP)- stimulated GTPase activity for K-Ras construct or a mutant thereof can be measured using EnzCheck phosphate assay system (Life Technologies). For example K-Ras WT, K-Ras D154Q mutant, K-Ras G12D mutant, K-Ras G12S mutant, and K-Ras G12D/D154Q mutant proteins (2.5 mg/ml) in buffer (20 mmol/L Tris, pH 8.0, 50 mM NaCl) are loaded with GTP at room temperature for 2 hours by exposing to exchange buffer containing EDTA. Proteins are buffer exchanged to assay buffer (30 mM Tris, pH 7.5, 1 mM DTT) and the concentration is adjusted to 2 mg/ml. GTP loading is verified by back extraction of nucleotide using 6M urea and evaluation of nucleotide peaks by HPLC using an ion-exchange column. The assay is performed in a clear 384-well plate (Costar) by combining GTP-loaded K-Ras proteins (50 mM final) with 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG) (200 mM final), and purine nucleotide phosphorylase (5 U/ml final). GTP hydrolysis is initiated by the addition of MgCl ₂ at a working concentration of 40 mM. For GAP stimulation, Ras p21 protein activator 1 (P120GAP) can be included at 50 mM. Absorbance at 360 nm can be measured every 8 to 15 s for 1,000 s at 20 ºC. Samples are tested with or without a subject compound disclosed herein including compounds exemplified in Table 1 to assess each compound’s ability to inhibit signaling of a given Ras protein (e.g., a given mutant Kras) of interest. EXAMPLE 7: Nucleotide exchange assay [00913] The ability of a compound of the present disclosure to inhibit a Ras protein signaling can be demonstrated by a reduced nucleotide exchange activity. This assay can be also used to assess a selective inhibition of a mutant Ras protein relative to a wildtype, or relative to a different mutant Ras protein. For example, 250 nM or 500 nM GDP-loaded K-Ras proteins (e.g., wildtype or a mutant thereof including those mentioned in Example 6), each is incubated with different concentrations of compounds (for example ~60 μΜ, ~20 μΜ, ~6.7 μΜ, ~2.2 μΜ, ~0.7 μΜ, ~0.2 μΜ subject compound). A control reaction without subject compound is also included. SOS1 (catalytic domain) protein is added to the K-Ras protein solution. The nucleotide exchange reaction is initiated by adding fluorescent labelled GDP (Guanosine 5’-Diphosphate, BODIPY™ FL 2’-(or-3’)-O-(N-(2-Aminoethyl) Urethane) to a final concentration of 0.36 μΜ. Fluorescence is measured every 30 s for 70 minutes at 490nm/515nm (excitation/emission) in a M1000Pro plate reader (Tecan). Data is exported and analyzed to calculate an IC50 using GraphPad Prism (GraphPad Software). Sample(s) can be tested with or without a subject compound disclosed herein, including compound(s) exemplified in Table 1, to assess compound’s ability to inhibit K-Ras signaling or its IC50 against a given Ras protein (e.g., a given mutant K-Ras) of interest. EXAMPLE 8: Testing for modification of Ras protein [00914] Test compounds are prepared as 10 mM stock solutions in DMSO (Fisher cat#BP231-100). KRAS protein (e.g., His-tagged GDP-loaded wildtype 1-169, His-tagged GDP-loaded G12C 1-169, His-tagged GDP-loaded G12D 1-169, or His-tagged GDP-loaded G12S 1-169) is diluted to ~2 µM in appropriate buffer (e.g., a Hepes buffer at physiological conditions). For testing KRAS modification, compounds are diluted to 50X final test concentration in DMSO in 96- well storage plates.1 µl of the diluted 50X compounds are added to appropriate wells in the PCR plate (Fisher cat#AB-0800). ~49 µl of the stock protein solution is added to each well of the 96-well PCR plate. Reactions are mixed carefully. The plate is sealed well with aluminum plate seal, and stored in drawer at room temperature for 24hrs.5 µl of 2% formic acid (Fisher cat#A117-50) in MilliQ H2O is then added to each well followed by mixing with a pipette. The plate is then resealed with aluminum seal and stored until mass spectrometry analysis. [00915] The extent of covalent modification of KRAS proteins is determined by liquid chromatography electrospray mass spectrometry analysis of the intact proteins on a Thermo Q-Exactive Plus mass spectrometer.20 µl of sample is injected onto a bioZen 3.6 µm Intact C4 column (Phenomenex cat#00B-4767-AN) placed in a column oven set to 40°C and separated using a suitable LC gradient from ~20% to ~60% solvent B. Solvent A is 0.1% formic acid and solvent B is 0.1% formic acid in acetonitrile. HESI source settings are set to 40, 5 and 1 for the sheath, auxiliary and sweep gas flow, respectively. The spray voltage is 4 kV, and the capillary temperature is 320°C. S-lens RF level is 50 and auxiliary gas heater temperature is set to 200°C. The mass spectrometry is acquired using a scan range from 650 to 1750 m/z using positive polarity at a mass resolution of 70,000, AGC target of 1e6 ions and maximum injection time of 250ms. The recorded protein mass spectrum is deconvoluted from the raw data file using Protein Deconvolution v4.0 (Thermo). The protein mass and adduct masses are exported with their peak intensities. The peak intensities for the unmodified and modified protein are used to calculate the percent covalent modification of the KRAS protein based on the following equation: %KRAS protein modification = ((KRAS-compound) / (KRAS) + (KRAS-Compound)) *100. Applying the method exemplified herein, subject compounds exhibit selective covalent labeling of for example, Ras G12D or Ras G12S or Ras G12C mutant relative to WT Ras. One or more exemplified compounds exhibited the ability to crosslink Kras mutant G12D and/or G12C greater than 0%, 10%, 20%, 30%, 40%, 50%, or even higher within 24 hours when assessed in the assay described above. [00916] One or more exemplified compounds disclosed herein in Table 1 exhibits covalent labeling of Kras G12D and/or Kras G12C by at least 5% as ascertained by the methods exemplified in this Example 8. Such compounds are listed in Table 3 below. Table 3. EXAMPLE 9: Ras cellular assay [00917] The ability of any compound of the present disclosure to inhibit a Ras protein signalling can be demonstrated by inhibiting growth of a given Kras mutant cells or a wildtype cell. For example, this assay can be also used to assess a selective growth inhibition of a mutant Ras protein relative to a wildtype, or relative to a different mutant Ras protein. a. Growth of cells with K-Ras G12C mutation [00918] MIA PaCa-2 (ATCC CRL-1420) and NCI-H1792 (ATCC CRL-5895) cell lines comprise a G12C mutation and can be used to assess Ras cellular signaling in vitro, e.g., in response to a subject inhibitor compound of the present disclosure. This cellular assay can also be used to discern selective inhibition of a subject compounds against certain types of Kras mutants, e.g., more potent inhibition against KrasG12D relative to KrasG12C mutant, by using MIA PaCa-2 (G12C driven tumor cell line) as a comparison. MIA PaCa-2 culture medium is prepared with DMEM/Ham's F12 (e.g., with stable Glutamine, 10% FCS, and 2.5% Horse Serum. NCI-H1792 culture medium is prepared with RPMI 1640 (e.g., with stable Glutamine) and 10% FCS. [00919] On a first day (e.g., Day 1), Softagar (Select Agar, Invitrogen, 3% in ddH ₂ 0 autoclaved) is boiled and tempered at 48 ºC. Appropriate culture medium (i.e., medium) is tempered to 37 ºC. Agar ( 3%) is diluted 1:5 in medium (=0.6%) and 50 mI/well plated into 96 well plates (Corning, #3904), then incubated at room temperature for agar solidification. A 3% agar is diluted to 0.25% in medium (1:12 dilution) and tempered at 42 ºC. Cells are trypsinized, counted, and tempered at 37 ºC. The cells (e.g., MIA PaCa-2 at about 125-150 cells, NCI-H1792 at about 1000 cells) are resuspended in 100 mL 0.25% Agar and plated, followed by incubation at room temperature for agar solidification. The wells are overlaid with 50 mL of the medium. Sister wells in a separate plate are plated for time zero determination. All plates are incubated overnight at 37 ºC and 5% CO ₂ . [00920] On a second day (e.g., Day 2), time zero values are measured. A 40 mL volume of Cell Titer 96 Aqueous Solution (Promega) is added to each well and incubated in the dark at 37 ºC and 5% CO ₂ . Absorption can be measured at 490 nm and reference wavelength 660 nm. DMSO-prediluted test compounds are added to wells of interest, e.g., with HP Dispenser, to one or more desired concentrations (e.g., a final DMSO concentration of 0.3%). [00921] On a tenth day (e.g., Day 10), absorption by wells treated with the test compounds and control wells are measured with, for example, Cell Titer 96 AQueous and analyzed in comparison to the time zero measurements. The IC50 values are determined using the four parameter fit. The resulting IC50 value is a measurement of the ability of the compounds herein to reduce cell growth of Ras-driven cells (e.g., tumor cell lines) in vitro and/or in vivo. b. Growth of cells with K-Ras G12D mutation [00922] ASPC-1 (ATCC CRL-1682), Panc-10.05 (ATCC CRL-2547), A427 cell lines comprise a G12D mutation and can be used to assess Ras cellular signaling in vitro, e.g., in response to the compounds herein. ASPC-1 culture medium is prepared with RPMI-1640 and 10% heat-inactivated FBS. Panc-10.05 culture medium is prepared with RPMI-1640, 10 Units/ml human recombinant insulin, and 10% FBS. A427 cell culture is prepared with RPMI-1640 and 10% heat-inactivated FBS. A CellTiter-Glo (CTG) luminescent based assay (Promega) is used to assess growth of the cells, as a measurement of the ability of the compounds herein to inhibit Ras signaling in the cells. The cells (e.g., 800 per well) are seeded in their respective culture medium in standard tissue culture-treated 384-well format plates (Falcon #08-772-116) or ultra-low attachment surface 384-well format plates (S-Bio # MS-9384UZ ). The day after plating, cells are treated with a dilution series (e.g., a 9 point 3-fold dilution series) of the compounds herein (e.g., approximately 40 µl final volume per well). Cell viability can be monitored (e.g., approximately 5 days later) according to the manufacturer’s recommended instructions, where the CellTiter-Glo reagent is added (e.g., approximately 10 µl), vigorously mixed, covered, and placed on a plate shaker (e.g., approximately for 20 min) to ensure sufficient cell lysis prior to assessment of luminescent signal. The IC50 values are determined using the four parameter fit. The resulting IC50 value is a measurement of the ability of the compounds herein to reduce cell growth of Ras-driven cells (e.g., tumor cell lines) in vitro and/or in vivo. The IC50 values are determined using the four parameter fit. The resulting IC50 value is a measurement of the ability of the compounds herein to reduce cell growth of Ras-driven cells (e.g., tumor cell lines) in vitro and/or in vivo. EXAMPLE 10: In vivo Ras inhibition [00923] The in vivo reduction in Ras signaling output by a compound of the present disclosure is determined in a mouse tumor xenograft model, particularly in a mutant K-Ras model utilizing cells including a mutant KRas (e.g., KRas G12D, KRas G12S, KRas G12C mutant) to generate a xenograft model comparable to the xenograft model exemplified below. Xenograft with K-Ras G12D mutation [00924] In another example, tumor xenografts are established by administration of tumor cells with K-Ras G12D mutation (e.g., ASPC-1 cells) or other mutant K-Ras expressing cells (e.g., K-Ras G12S or K-Ras G12C), into mice. Female 6- to 8-week-old athymic BALB/c nude (NCr) nu/nu mice are used for xenografts. The tumor cells (e.g., approximately 5x10 ⁶ ) are harvested on the day of use and injected in growth-factor-reduced Matrigel/PBS (e.g., 50% final concentration in 100 µl). One flank is inoculated subcutaneously per mouse. Mice are monitored daily, weighed twice weekly, and caliper measurements begin when tumors become visible. For efficacy studies, animals are randomly assigned to treatment groups by an algorithm that assigns animals to groups to achieve best case distributions of mean tumor size with lowest possible standard deviation. Tumor volume can be calculated by measuring two perpendicular diameters using the following formula: (L x w ² ) / 2 in which L and w refer to the length and width tumor diameter, respectively. Percent tumor volume change can be calculated using the following formula: (V _final –V _initial )/V _initial x 100. Percent of tumor growth inhibition (%TGI) can be calculated using the following formula: %TGI = 100 x (1 – (average V _final –V _initial of treatment group) / (average V _final –V _initial of control group). When tumors reach a threshold average size (e.g., approximately 200-400 mm ³ ). mice are randomized into 3-10 mice per group and are treated with vehicle (e.g., 100% Labrasol®) or a subject compound disclosed herein using, for example, a daily schedule by oral gavage. Results can be expressed as mean and standard deviation of the mean.