CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and benefit of U.S. Provisional Patent Application No. 63/283,138, filed November 24, 2021, and U.S. Provisional Patent Application No. 63/344,025, filed May 19, 2022, the disclosures of which are hereby incorporated herein by reference in their entireties.

SUBMISSION OF ELECTRONIC SEQUENCE LISTING

[0002] The ccoonntteenntt ooff tthhee eelleeccttrroonniicc Sequence Listing (file name: 146392054840SeqList.xml, date created: November 17, 2022, size: 20,029 bytes) is herein incorporated by reference in its entirety.

FIELD OF THE DISCLOSURE

[0003] The present disclosure relates to compounds useful for therapy and/or prophylaxis in a mammal, and in particular as inhibitors of TEAD useful for treating cancer.

BRIEF DESCRIPTION

[0004] The Hippo pathway is a signaling pathway that regulates cell proliferation and cell death and determines organ size. The pathway is believed to play a role as a tumor suppressor in mammals, and disorders of the pathway are often detected in human cancers. The pathway is involved in and/or may regulate the self-renewal and differentiation of stem cells and progenitor cells. In addition, the Hippo pathway may be involved in wound healing and tissue regeneration. Furthermore, it is believed that as the Hippo pathway cross-talks with other signaling pathways such as Wnt, Notch, Hedgehog, and MAPK/ERK, it may influence a wide variety of biological events, and that its dysfunction could be involved in many human diseases in addition to cancer. For reviews, see, for example, Halder et al., 2011, Development 138:9-22; Zhao et al., 2011, Nature Cell Biology 13:877-883; Bao et al., 2011, J. Biochem. 149:361-379; Zhao at al., 2010, J. Cell Sci. 123:4001-4006.

[0005] The Hippo signaling pathway is conserved from drosophila to mammals (Vassilev et al., Genes and Development, 2001, 15, 1229-1241; Zeng and Hong, Cancer Cell, 2008, 13, 188- 192). The core of the pathway consists of a cascade of kinases (Hippo-MSTl-2 being upstream of Lats 1-2 and NDRI-2) leading to the phosphorylation of two transcriptional co-activators, YAP (Yes-Associated Protein) and TAZ (Transcription co-activator with PDZ binding motif or taf azzin;

Zhao et al., Cancer Res., 2009, 69, 1089-1098; Lei et al., Mol. Cell. Biol., 2008, 28, 2426-2436).

[0006] Because the Hippo signaling pathway is a regulator of animal development, organ size control and stem cell regulation, it has been implicated in cancer development (Review in Harvey et al., Nat. Rev. Cancer, 2013, 13, 246-257; Zhao et al., Genes Dev. 2010, 24, 862-874). In vitro, the overexpression of YAP or TAZ in mammary epithelial cells induces cell transformation, through interaction of both proteins with the TEAD family of transcription factors. Increased YAP/TAZ transcriptional activity induces oncogenic properties such as epithelial- mesenchymal transition and was also shown to confer stem cells properties to breast cancer cells. In vivo, in mouse liver, the overexpression of YAP or the genetic knockout of its upstream regulators MST1-2 triggers the development of hepatocellular carcinomas. Furthermore, when the tumor suppressor NF2 is inactivated in the mouse liver, the development of hepatocellular carcinomas can be blocked completely by the co-inactivation of YAP.

[0007] It is believed that deregulation of the Hippo tumor suppressor pathway is a major event in the development of a wide range of malignancies, including with no limitations, lung cancer (NSCLC; Zhou et al., Oncogene, 2011, 30, 2181-2186; Wang et al., Cancer Sci., 2010, 101, 1279-1285), breast cancer (Chan et al., Cancer Res., 2008, 68, 2592-2598; Lamar et al., Proc. Natl. Acad. Sci, USA, 2012; 109, E2441-E2250; Wang et al., Eur. J. Cancer, 2012, 48, 1227-1234), head and neck cancer (Gasparotto et al., Oncotarget., 2011, 2, 1165-1175; Steinmann et al., Oncol. Rep., 2009, 22, 1519-1526), colon cancer (Angela et al., Hum. Pathol., 2008, 39, 1582-1589; Yuen et al., PLoS One, 2013, 8, e54211; Avruch et al., Cell Cycle, 2012, 11, 1090-1096), ovarian cancer (Angela et al., Hum. Pathol., 2008, 39, 1582-1589; Chad et al., Cancer Res., 2010, 70, 8517-8525; Hall et al., Cancer Res., 2010, 70, 8517-8525), liver cancer (Jie et al., Gastroenterol. Res. Pract., 2013, 2013, 187070; Ahn et al., Mol. Cancer. Res., 2013, 11, 748-758; Liu et al., Expert. Opin. Ther. Targets, 2012, 16, 243-247), brain cancer (Orr et al., J Neuropathol. Exp. Neurol. 2011, 70, 568-577; Baia et al., Mol. Cancer Res., 2012, 10, 904-913; Striedinger et al., Neoplasia, 2008, 10, 1204-1212) and prostate cancer (Zhao et al., Genes Dev., 2012, 26, 54-68; Zhao et al., Genes Dev., 2007, 21, 2747-2761), mesotheliomas (Fujii et al., J. Exp. Med., 2012, 209, 479-494; Mizuno et al., Oncogene, 2012, 31, 5117-5122; Sekido Y., Pathol. Int., 2011, 61, 331-344), sarcomas (Seidel et al., Mol. Carcinog., 2007, 46, 865-871) and leukemia (Jimenez-Velasco et al., Leukemia, 2005, 19, 2347-2350). [0008] Two of the core components of the mammalian Hippo pathway are Lats1 and Lats2, which are nuclear Dbf2-related (NDR) family protein kinases homologous to Drosophila Warts (Wts). The Eats 1/2 proteins are activated by association with the scaffold proteins Mob1A/B (Mps one binder kinase activator-like 1A and 1B), which are homologous to Drosophila Mats. Lats1/2 proteins are also activated by phosphorylation by the STE20 family protein kinases Mstl and Mst2, which are homologous to Drosophila Hippo. Lats1/2 kinases phosphorylate the downstream effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif; WWTR1), which are homologous to Drosophila Yorkie. The phosphorylation of YAP and TAZ by Lats1/2 are crucial events within the Hippo signaling pathway. Lats1/2 phosphorylates YAP at multiple sites, but phosphorylation of Ser127 is critical for YAP inhibition. Phosphorylation of YAP generates a protein-binding motif for the 14-3-3 family of proteins, which upon binding of a 14-3-3 protein, leads to retention and/or sequestration of YAP in the cell cytoplasm. Likewise, Lats1/2 phosphorylates TAZ at multiple sites, but phosphorylation of Ser89 is critical for TAZ inhibition. Phosphorylation of TAZ leads to retention and/or sequestration of TAZ in the cell cytoplasm. In addition, phosphorylation of YAP and TAZ is believed to destabilize these proteins by activating phosphorylation-dependent degradation catalyzed by YAP or TAZ ubiquitination. Thus, when the Hippo pathway is “on”, YAP and/or TAZ is phosphorylated, inactive, and generally sequestered in the cytoplasm; in contrast, when the Hippo pathway is “off’, YAP and/or TAZ is non-phosphorylated, active, and generally found in the nucleus.

[0009] Non-phosphorylated, activated YAP is translocated into the cell nucleus where its major target transcription factors are the four proteins of the TEAD-domain-containing family (TEAD1-TEAD4, collectively “TEAD”). YAP together with TEAD (or other transcription factors such as Smadl, RUNX, ErbB4 and p73) has been shown to induce the expression of a variety of genes, including connective tissue growth factor (CTGF), Gli2, Birc5, Birc2, fibroblast growth factor 1 (FGF1), and amphiregulin (AREG). Like YAP, non-phosphorylated TAZ is translocated into the cell nucleus where it interacts with multiple DNA-binding transcription factors, such as peroxisome proliferator-activated receptor y (PPARy), thyroid transcription factor-1 (TTF-1), Pax3, TBX5, RUNX, TEAD1 and Smad2/3/4. Many of the genes activated by YAP/TAZ- transcription factor complexes mediate cell survival and proliferation. Therefore, under some conditions YAP and/or TAZ acts as an oncogene and the Hippo pathway acts as a tumor suppressor. Hence, pharmacological targeting of the Hippo cascade through inhibition of TEAD would be valuable approach for the treatment of cancers that harbor functional alterations of this pathway. Certain TEAD inhibitors have been shown to be associated with increased risk of adverse events such as cardiac arrhythmias due to off-target sodium channel inhibition. Thus, there is a need for TEAD inhibitors with reduced risk of adverse events.

[0010] Ras is a small GTP -binding protein that functions as a nucleotide-dependent switch for central growth signaling pathways. In response to extracellular signals, Ras is converted from a GDP-bound (Ras ^GDP ) to a GTP -bound (Ras ^GTP ) state, as catalyzed by guanine nucleotide exchange factors (GEFs), notably the S0S1 protein. Active Ras ^GTP mediates its diverse growth- stimulating functions through its direct interactions with effectors including Raf, PI3K, and Rai guanine nucleotide dissociation stimulator. The intrinsic GTPase activity of Ras then hydrolyzes GTP to GDP to terminate Ras signaling. The Ras GTPase activity can be further accelerated by its interactions with GTPase-activating proteins (GAPs), including the neurofibromin 1 tumor suppressor.

[0011] Mutant Ras has a reduced GTPase activity, which prolongs its activated conformation, thereby promoting Ras-dependent signaling and cancer cell survival or growth. Mutation in Ras which affects its ability to interact with GAP or to convert GTP back to GDP will result in a prolonged activation of the protein and consequently a prolonged signal to the cell telling it to continue to grow and divide. Because these signals result in cell growth and division, overactive RAS signaling may ultimately lead to cancer. Mutations in any one of the three main isoforms of RAS (H-Ras, N-Ras, or K-Ras) genes are common events in human tumorigenesis. Among the three Ras isoforms (K, N, and H), K-Ras is most frequently mutated.

[0012] The most common K-Ras (or KRAS) mutations are found at residue G12 and G13 in the P-loop and at residue Q61. G12C is a frequent mutation of K-Ras gene (glycine-12 to cysteine). G12C is a single point mutation with a glycine-to-cysteine substitution at codon 12. This substitution favors the activated state of KRAS, amplifying signaling pathways that lead to oncogenesis (see, e.g., Hallin et al. (Cancer Di scov, 2020, 10(1): 54-71), Skoulidis et al. (N. Engl. J. Med., 2021, 384(25): 2371-2381), and Hong et al. (N. Engl. J. Med., 2020, 383(13): 1207- 1217)). G12D, G12V, and G13D are other frequent mutations. Mutations of Ras in cancer are associated with poor prognosis.

[0013] Inactivation of oncogenic Ras in mice results in tumor shrinkage. Thus, Ras is widely considered an oncology target of exceptional importance. However, treatment with inhibitors of Ras (for example, KRAS) can lead to resistance through bypass of KRAS/MAPK pathway dependence, and activation of the Hippo pathway. [0014] There is, therefore, a need for therapies that improve the ability of inhibitors of Ras (for example, KRAS) and inhibitors of YAP, TAZ, TEAD, and/or the YAP:TEAD protein-protein interaction to treat a range of diseases, disorders, and conditions, including cancer.

SUMMARY OF THE DISCLOSURE

[0015] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-AB) is provided: or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

L’ is selected from the group consisting of *-N(R ¹ )-L-** and , wherein * denotes the point of attachment to Z, and ** denotes the point of attachment to

R ¹ is H or C _1-6 alkyl;

X ¹ is N or CR ^s , wherein R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e ; wherein each of R ^d , R ^e and R ^f are independently H, C _1-6 alkyl, or C _3-20 cycloalkyl, wherein each of C _1-6 alkyl and C _3-20 cycloalkyl are independently optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -OR ^f1 , -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^fl is -C(O)CH ₂ NR ^d R ^e , -C(O)C _{1- 6} alkyl, -P(O)(OH) ₂ ; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _{1- 6} alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, 3 to 6 membered heterocyclyl, C _{3- 6} cycloalkyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH, C _1-6 alkoxyl, halo, oxo, -S(O) ₂ CH ₃ , or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N, CH, or CD, provided that: 1) only one of X ¹ , X ² , X ³ , and X ⁴ is N; or 2) X ¹ is N, X ² is CH, X ³ is CH, and X ⁴ is N; or 3) X ¹ is CR ^s and X ² , X ³ , and X ⁴ are each independently CH or CD;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _1-6 alkynyl optionally substituted with -OH; or R ^x is cyclobutenyl, dihydrofuranyl, bicyclobutanyl, or cyclopentenyl; or

Z is S(O) ₂ R ^x1 , whereinR ^x1 is C _2-6 alkenyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each 1; or n and m are each 2.

[0016] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (AB) is provided: wherein:

L' is selected from the group consisting of *-N(R ¹ )-L-** and , wherein * denotes the point of attachment to Z, and ** denotes the point of attachment to

R ¹ is H or C _1-6 alkyl;

X ¹ is N or CR ^s , wherein R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e ; wherein each of R ^d , R ^e and R ^f are independently H, C _1-6 alkyl, or C _3-20 cycloalkyl, wherein each of C _1-6 alkyl and C _3-20 cycloalkyl are independently optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or-CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl;

X ² , X ³ , and X ⁴ are each independently N, CH, or CD, provided that only one of X ¹ , X ² , X ³ , and X ⁴ isN;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _1-6 alkynyl optionally substituted with -OH; or R ^x is cyclobutenyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each 1; or n and m are each 2.

[0017] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A) or (B) is provided:

wherein:

R ¹ is H or C _1-6 alkyl;

X ¹ is N or CR ^s , wherein R ^s is selected from H, -CN, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, C _1-15 alkoxy, -NR ^d COR ^e , - CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, -OH, - CN, and C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N or CH, provided that only one of X ¹ , X ² , X ³ , and X ⁴ is N; B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl and halo; or wherein R ^x is C _1-6 alkyl, optionally substituted with one or more halo;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each independently 1 or 2.

[0018] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A’) or (B’) is provided: wherein:

X ¹ is N or CR ^s , wherein R ^s is selected from H, -CN, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, C _1-15 alkoxy, NR ^d COR ^e , - CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, -OH, - CN, and C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N or CH, provided that only one of X ¹ , X ² , X ³ , and X ⁴ is N;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl and halo; or wherein R ^x is C _1-6 alkyl, optionally substituted with one or more halo;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each independently 1 or 2.

[0019] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A) or (I-B) is provided:

wherein:

X ¹ is N or CR ^s , wherein R ^s is selected from H, -CN, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, C _1-15 alkoxy, NR ^d COR ^e , - CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, -OH, - CN, and C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N or CH, provided that only one of X ¹ , X ² , X ³ , and X ⁴ is N;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of

B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

R ^a , R ^b , and R ^c are each independently H, halo, or C _1-5 alkyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each independently 1 or 2.

[0020] In some aspects, a pharmaceutical composition comprising a compound of formula (A) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided.

[0021] In some aspects, a pharmaceutical composition comprising a compound of formula

(B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided.

[0022] In some aspects, a pharmaceutical composition comprising a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided.

[0023] In some aspects, a pharmaceutical composition comprising a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided.

[0024] In some aspects, a pharmaceutical composition comprising a compound of formula (A’) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided.

[0025] In some aspects, a pharmaceutical composition comprising a compound of formula (B’) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided.

[0026] In some aspects, a pharmaceutical composition comprising a compound of formula (I-A) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided. [0027] In some aspects, a pharmaceutical composition comprising a compound of formula (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided.

[0028] In some aspects, a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use in medical therapy.

[0029] In some aspects, a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use in medical therapy.

[0030] In some aspects, a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use in medical therapy.

[0031] In some aspects, a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of cancer.

[0032] In some aspects, a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of cancer.

[0033] In some aspects, a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of cancer.

[0034] In some aspects, a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the preparation of a medicament for the treatment or prophylaxis of cancer.

[0035] In some aspects, a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the preparation of a medicament for the treatment or prophylaxis of cancer.

[0036] In some aspects, a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the preparation of a medicament for the treatment or prophylaxis of cancer. [0037] In some aspects, a method for treating cancer in a mammal is provided, the method comprising, administering a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal.

[0038] In some aspects, a method for treating cancer in a mammal is provided, the method comprising, administering a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal.

[0039] In some aspects, a method for treating cancer in a mammal is provided, the method comprising, administering a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal.

[0040] In some aspects, a method for treating cancer in a mammal is provided, the method comprising administering a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal in combination with a second therapeutic agent.

[0041] In some aspects, a method for treating cancer in a mammal is provided, the method comprising administering a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal in combination with a second therapeutic agent.

[0042] In some aspects, a method for treating cancer in a mammal is provided, the method comprising administering a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal in combination with a second therapeutic agent.

[0043] In some aspects, a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for modulating TEAD activity.

[0044] In some aspects, a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for modulating TEAD activity.

[0045] In some aspects, a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for modulating TEAD activity. [0046] In some aspects, a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of a disease or condition mediated by TEAD activity.

[0047] In some aspects, a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of a disease or condition mediated by TEAD activity.

[0048] In some aspects, a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of a disease or condition mediated by TEAD activity.

[0049] In some aspects, a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use for the preparation of a medicament for the treatment or prophylaxis of a disease or condition that is mediated by TEAD activity.

[0050] In some aspects, a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use for the preparation of a medicament for the treatment or prophylaxis of a disease or condition that is mediated by TEAD activity.

[0051] In some aspects, a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use for the preparation of a medicament for the treatment or prophylaxis of a disease or condition that is mediated by TEAD activity.

[0052] In some aspects, a method for modulating TEAD activity is provided, the method comprising contacting TEAD with a therapeutically effective amount of a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.

[0053] In some aspects, a method for modulating TEAD activity is provided, the method comprising contacting TEAD with a therapeutically effective amount of a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.

[0054] In some aspects, a method for modulating TEAD activity is provided, the method comprising contacting TEAD with a therapeutically effective amount of a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0055] In some aspects, a method for treating a disease or condition mediated by TEAD activity in a mammal is provided, the method comprising administering a compound of formula (A), (B), (A’), (B’), (I-A), or (I-B) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal.

[0056] In some aspects, a method for treating a disease or condition mediated by TEAD activity in a mammal is provided, the method comprising administering a compound of formula (AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal.

[0057] In some aspects, a method for treating a disease or condition mediated by TEAD activity in a mammal is provided, the method comprising administering a compound of formula (I-AB) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal.

[0058] In one aspect, the present disclosure is directed to a combination comprising: (i) one or more YAP/TAZ-TEAD inhibitors; and (ii) one or more KRAS inhibitors. In some aspects, one or more YAP/TAZ-TEAD inhibitors and one or more KRAS inhibitors are co-administered to an individual. In some aspects, the combination is administered to an individual in the same composition. In some aspects, the combination is administered to an individual in different compositions. Thus, it is understood that the one or more YAP/TAZ-TEAD inhibitors and the one or more KRAS inhibitors may be administered simultaneously or sequentially to the individual. In some aspects, provided herein are compositions comprising one or more YAP/TAZ-TEAD inhibitors and one or more KRAS inhibitors. In another aspect, the present disclosure is directed to methods of modulating or inhibiting KRAS activity in a cell, comprising administering to the cell an effective amount of such combinations. In another aspect, the present disclosure is directed to methods of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of such combinations. In another aspect, the present disclosure is directed to methods of reducing resistance of a subject to treatment comprising a KRAS inhibitor, wherein the method comprises administering to the subject a therapeutically effective amount of a TEAD inhibitor.

[0059] In one aspect, the present disclosure is directed to processes of preparing one or more TEAD inhibitors described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[0060] The following embodiments are representative of some aspects of the disclosure. [0061] FIGURE 1 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor).

[0062] FIGURE 2 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor).

[0063] FIGURE 3 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor).

[0064] FIGURE 4 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0065] FIGURE 5 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0066] FIGURE 6 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0067] FIGURE 7 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0068] FIGURE 8 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0069] FIGURE 9 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0070] FIGURE 10 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor). [0071] FIGURE 11 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor).

[0072] FIGURE 12 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor).

[0073] FIGURE 13 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0074] FIGURE 14 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0075] FIGURE 15 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0076] FIGURE 16 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0077] FIGURE 17 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0078] FIGURE 18 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0079] FIGURE 19 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor).

[0080] FIGURE 20 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor). [0081] FIGURE 21 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K1 (a KRAS inhibitor).

[0082] FIGURE 22 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0083] FIGURE 23 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0084] FIGURE 24 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K2 (a KRAS inhibitor).

[0085] FIGURE 25 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0086] FIGURE 26 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0087] FIGURE 27 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K3 (a KRAS inhibitor).

[0088] FIGURE 28 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0089] FIGURE 29 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0090] FIGURE 30 depicts % inhibition of H2030 cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor). [0091] FIGURE 31 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0092] FIGURE 32 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0093] FIGURE 33 depicts % inhibition of H358 parental cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0094] FIGURE 34 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T1 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0095] FIGURE 35 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T2 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0096] FIGURE 36 depicts % inhibition of H358 resistant cells (KRAS G12C) following administration of a combination comprising Compound T3 (a YAP/TAZ-TEAD inhibitor) and Compound K4 (a KRAS inhibitor).

[0097] FIGURE 37 depicts tumor volume over time of mice inoculated with NCI-H2122 cells; MC 0.5% PO QDx21 + MCT PO BIDx21.

[0098] FIGURE 38 depicts tumor volume over time of mice inoculated with NCI-H2122 cells; Compound K425 mg/kg PO QDx21.

[0099] FIGURE 39 depicts tumor volume over time of mice inoculated with NCI-H2122 cells; Compound T1 10 mg/kg PO BIDx21.

[0100] FIGURE 40 depicts tumor volume over time of mice inoculated with NCI-H2122 cells; Compound T1 20 mg/kg PO QDx21

[0101] FIGURE 41 depicts tumor volume over time of mice inoculated with NCI-H2122 cells; Compound K425 mg/kg PO QDx21 and Compound T1 10 mg/kg PO BIDx21.

[0102] FIGURE 42 depicts tumor volume over time of mice inoculated with NCI-H2122 cells; Compound K425 mg/kg PO QDx21 and Compound T1 20 mg/kg PO QDx21. [0103] FIGURE 43 depicts body weight change % over time of mice inoculated with NCI-H2122 cells; MC 0.5% PO QDx21 + MCT PO BIDx21.

[0104] FIGURE 44 depicts body weight change % over time of mice inoculated with NCI-H2122 cells; Compound K425 mg/kg PO QDx21.

[0105] FIGURE 45 depicts body weight change % over time of mice inoculated with NCI-H2122 cells; Compound T1 10 mg/kg PO BIDx21.

[0106] FIGURE 46 depicts body weight change % over time of mice inoculated with NCI-H2122 cells; Compound T1 20 mg/kg PO QDx21.

[0107] FIGURE 47 depicts body weight change % over time of mice inoculated with NCI-H2122 cells; Compound K425 mg/kg PO QDx21 and Compound T1 10 mg/kg PO BIDx21.

[0108] FIGURE 48 depicts body weight change % over time of mice inoculated with NCI-H2122 cells; Compound K425 mg/kg PO QDx21 and Compound T1 20 mg/kg PO QDx21.

DETAILED DESCRIPTION

DEFINITIONS

[0109] Unless otherwise indicated, the following specific terms and phrases used in the description and claims are defined as follows.

[0110] The term “moiety” refers to an atom or group of chemically bonded atoms that is attached to another atom or molecule by one or more chemical bonds thereby forming part of a molecule.

[0111] The term “substituted” refers to the fact that at least one of the hydrogen atoms of that moiety is replaced by another substituent or moiety.

[0112] The term “alkyl” refers to an aliphatic straight-chain or branched-chain saturated hydrocarbon moiety having 1 to 20 carbon atoms, such as 1 to 12 carbon atoms, or 1 to 6 carbon atoms. Alkyl groups may be optionally substituted. In some embodiments, alkyl is unsubstituted.

[0113] In some embodiments, “alkoxy” is -O-alkyl.

[0114] The term “cycloalkyl” means a saturated or partially unsaturated carbocyclic moiety having mono- or bicyclic (including bridged bicyclic) rings and 3 to 10 carbon atoms in the ring. In particular aspects, cycloalkyl may contain from 3 to 8 carbon atoms (i.e., (C _3- C ₈ )cycloalkyl). In other particular aspects cycloalkyl may contain from 3 to 6 carbon atoms (i.e., (C ₃ -C ₆ )cycloalkyl). Examples of cycloalkyl moieties include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and partially unsaturated (cycloalkenyl) derivatives thereof (e.g. cyclopentenyl, cyclohexenyl, and cycloheptenyl). The cycloalkyl moiety can be attached in a spirocycle fashion such as spirocyclopropyl:

[0115] The term “haloalkyl” refers to an alkyl group wherein one or more of the hydrogen atoms of the alkyl group has been replaced by the same or different halogen atoms, such as fluoro atoms. Examples of haloalkyl include monofluoro-, difluoro- or trifluoro-methyl, -ethyl or - propyl, for example 3,3,3-trifluoropropyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, fluoromethyl, or trifluoromethyl. Haloalkyl groups may be optionally substituted. In some embodiments, haloalkyl is unsubstituted.

[0116] The term “alkenyl” refers to a straight or branched chain alkyl or substituted alkyl group as defined elsewhere herein having at least one carbon-carbon double bond. Alkenyl groups may be optionally substituted. In some embodiments, alkenyl is unsubstituted.

[0117] The term “alkynyl” refers to a straight or branched chain alkyl or substituted alkyl group as defined elsewhere herein having at least one carbon-carbon triple bond. Alkynyl groups may be optionally substituted. In some embodiments, alkynyl is unsubstituted.

[0118] The terms “heterocyclyl” and “heterocycle” refer to a 4, 5, 6 and 7-membered monocyclic or 7, 8, 9 and 10-membered bicyclic (including bridged bicyclic) heterocyclic moiety that is saturated or partially unsaturated, and has one or more (e.g., 1, 2, 3 or 4) heteroatoms selected from oxygen, nitrogen and sulfur in the ring with the remaining ring atoms being carbon. When used in reference to a ring atom of a heterocycle, a nitrogen or sulfur may also be in an oxidized form, and a nitrogen may be substituted. The heterocycle can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocycles include, without limitation, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazolyl, thiazepinyl, morpholinyl, and quinuclidinyl. The term heterocycle also includes groups in which a heterocycle is fused to one or more aryl, heteroaryl, or cycloalkyl rings, such as benzothiazolyl, benzofuranyl, furopyridinyl, indolinyl, 3H-indolyl, chromanyl, 2- azabicyclo[2.2.1]heptanyl, octahydroindolyl, or tetrahydroquinolinyl. Heterocyclyl groups may be optionally substituted. In some embodiments, heterocyclyl is unsubstituted. [0119] The term “aryl” refers to a cyclic aromatic hydrocarbon moiety having a mono-, bi- or tricyclic aromatic ring of 5 to 20 carbon ring atoms. Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, benzyl, and the like. The term “aryl” also includes partially hydrogenated derivatives of the cyclic aromatic hydrocarbon moiety provided that at least one ring of the cyclic aromatic hydrocarbon moiety is aromatic, each being optionally substituted. In some aspects, monocyclic aryl rings may have 5 or 6 carbon ring atoms. Aryl groups may be optionally substituted. In some embodiments, aryl is unsubstituted.

[0120] The term “heteroaryl” refers an aromatic heterocyclic mono- or bicyclic ring system of 1 to 20 ring atoms, comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, the remaining ring atoms being carbon. Examples of heteroaryl moieties include pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, triazinyl, isoxazolyl, benzofuranyl, isothiazolyl, benzothienyl, indolyl, isoindolyl, isobenzofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzooxadi azolyl, benzothiadiazolyl, benzotriazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl, or quinoxalinyl. Heteroaryl groups may be optionally substituted. In some embodiments, heteroaryl is unsubstituted.

[0121] The terms “halo” and “halogen” refer fluoro, chloro, bromo and iodo. In some aspects, halo is fluoro or chloro.

[0122] The term “oxo” refers to the =O moiety.

[0123] The term “cyano” refers to the -C=N moiety.

[0124] The terms “spirocycle” and “spirocyclyl” refer to carbogenic bicyclic ring systems comprising between 5 and 13 carbon atoms with both rings connected through a single atom. The rings can be different in size and nature, or identical in size and nature. Examples include spiropentane, spirohexane, spiroheptane, spirooctane, spirononane, or spirodecane. One or more of the carbon atoms in the spirocycle can be substituted with a heteroatom (e.g., O, N, S, or P). Spirocycle groups may be optionally substituted.

[0125] In some embodiments, the spirocycle is unsubstituted.

[0126] The term “pharmaceutically acceptable salts” refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undesirable. Salts may be formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, preferably hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, salicylic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p- toluenesulfonic acid, N-acetylcystein and the like. In addition, salts may be prepared by the addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, and magnesium 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, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N- ethylpiperidine, piperidine, polyamine resins and the like.

[0127] The term “prodrug” refers to those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present disclosure. Additionally, prodrugs can be converted to the compounds of the present disclosure by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present disclosure when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.

[0128] In some prodrug aspects, prodrugs include compounds wherein an amino acid residue, or a polypeptide chain of two or more (e.g., two, three or four) amino acid residues, is covalently joined through an amide or ester bond to a free amino, hydroxy or carboxylic acid group of a compound of the present disclosure. The amino acid residues include but are not limited to the 20 naturally occurring amino acids commonly designated by three letter symbols and also includes phosphoserine, phosphothreonine, phosphotyrosine, 4-hydroxyproline, hydroxylysine, demosine, isodemosine, gamma-carboxyglutamate, hippuric acid, octahydroindole-2-carboxylic acid, statine, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, penicillamine, ornithine, 3- methylhistidine, norvaline, beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, methyl-alanine, para-benzoylphenylalanine, phenylglycine, propargylglycine, sarcosine, methionine sulfone and tert-butylglycine.

[0129] In some other prodrug aspects, a free carboxyl group of a compound of the disclosure can be derivatized as an amide or alkyl ester. In yet other prodrug aspects, prodrugs comprising free hydroxy groups can be derivatized as prodrugs by converting the hydroxy group into a group such as, but not limited to, a phosphate ester, hemi succinate, dimethylaminoacetate, or phosphoryloxymethyloxy carbonyl group, as outlined in Fleisher, D. et al., (1996) Improved oral drug delivery: solubility limitations overcome by the use of prodrugs Advanced Drug Delivery Reviews, 19:115. Carbamate prodrugs of hydroxy and amino groups are also included, as are carbonate prodrugs, sulfonate esters and sulfate esters of hydroxy groups. Derivatization of hydroxy groups as (acyloxy)methyl and (acyloxy)ethyl ethers, wherein the acyl group can be an alkyl ester optionally substituted with groups including, but not limited to, ether, amine and carboxylic acid functionalities, or where the acyl group is an amino acid ester as described above, are also encompassed. Prodrugs of this type are described in J. Med. Chem., (1996), 39:10. More specific examples include replacement of the hydrogen atom of the alcohol group with a group such aass (C _1-6 )alkanoyloxymethyl, 1-((C _1-6 )alkanoyloxy)ethyl, 1 -methyl-1-((C _1-

₆ )alkanoyloxy)ethyl, (C _1-6 )alkoxy carbonyloxymethyl, N-(C _1-6 )alkoxycarbonylaminomethyl, succinoyl, (C _1-6 )alkanoyl, alpha-amino(C _1-4 )alkanoyl, arylacyl and alpha-aminoacyl, or alpha- aminoacyl-alpha-aminoacyl, where each alpha-aminoacyl group is independently selected from the naturally occurring L-amino acids, P(O)(OH) ₂ , -P(O)(O(C _1-6 )alkyl) ₂ or glycosyl (the radical resulting from the removal of a hydroxyl group of the hemiacetal form of a carbohydrate).

[0130] For additional examples of prodrug derivatives, see, for example, a) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985) and Methods in Enzymology, Vol. 42, p. 309- 396, edited by K. Widder, et al. (Academic Press, 1985); b) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 “Design and Application of Prodrugs,” by H. Bundgaard p. 113-191 (1991); c) H. Bundgaard, Advanced Drug Delivery Reviews, 8:1-38 (1992); d) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77:285 (1988); and e) N. Kakeya, et al., Chem. Pharm. Bull., 32:692 (1984), each of which is specifically incorporated herein by reference.

[0131] Additionally, the present disclosure provides for metabolites of compounds of the disclosure. As used herein, a “metabolite” refers to a product produced through metabolism in the body of a specified compound or salt thereof. Such products can result for example from the oxidation, reduction, hydrolysis, amidation, deamidation, esterification, deesterification, enzymatic cleavage, and the like, of the administered compound.

[0132] Metabolite products typically are identified by preparing a radiolabeled (e.g., ¹⁴ C or ³ H) isotope of a compound of the disclosure, administering it parenterally in a detectable dose (e.g., greater than about 0.5 mg/kg) to an animal such as rat, mouse, guinea pig, monkey, or to man, allowing sufficient time for metabolism to occur (typically about 30 seconds to 30 hours) and isolating its conversion products from the urine, blood or other biological samples. These products are easily isolated since they are labeled (others are isolated by the use of antibodies capable of binding epitopes surviving in the metabolite). The metabolite structures are determined in conventional fashion, e.g., by MS, LC/MS or NMR analysis. In general, analysis of metabolites is done in the same way as conventional drug metabolism studies well known to those skilled in the art. The metabolite products, so long as they are not otherwise found in vivo, are useful in diagnostic assays for therapeutic dosing of the compounds of the disclosure.

[0133] Certain compounds of the present disclosure can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present disclosure. Certain compounds of the present disclosure can exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present disclosure and are intended to be within the scope of the present disclosure.

[0134] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers.” Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers.” Diastereomers are stereoisomers with opposite configuration at one or more chiral centers which are not enantiomers. Stereoisomers bearing one or more asymmetric centers that are non-superimposable mirror images of each other are termed “enantiomers.” When a compound has an asymmetric center, for example, if a carbon atom is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center or centers and is described by the R- and S-sequencing rules of Cahn, Ingold and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. In certain aspects the compound is enriched by at least about 90% by weight with a single diastereomer or enantiomer. In other aspects the compound is enriched by at least about 95%, 98%, or 99% by weight with a single diastereomer or enantiomer.

[0135] Certain compounds of the present disclosure possess asymmetric carbon atoms (optical centers) or double bonds; the racemates, diastereomers, geometric isomers, regioisomers and individual isomers (e.g., separate enantiomers) are all intended to be encompassed within the scope of the present disclosure.

[0136] The compounds of the present disclosure may also exist in different tautomeric forms, and all such forms are embraced within the scope of the disclosure. The term “tautomer” or “tautomeric form” refers to structural isomers of different energies which are interconvertible via a low energy barrier. For example, proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol and imine-enamine isomerizations. Valence tautomers include interconversions by reorganization of some of the bonding electrons.

[0137] Unless otherwise indicated, the term “a compound of the formula” or “a compound of formula” or “compounds of the formula” or “compounds of formula” refers to any compound selected from the genus of compounds as defined by the formula. In some embodiments or aspects, the term also includes a pharmaceutically acceptable salt or ester of any such compound, a stereoisomer, or a tautomer of such compound.

[0138] The term“a therapeutically effective amounf’of a compound means an amount of compound that is effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is within the skill in the art. The therapeutically effective amount or dosage of a compound according to this disclosure can vary within wide limits and may be determined in a manner known in the art. Such dosage will be adjusted to the individual requirements in each particular case including the specific compound(s) being administered, the route of administration, the condition being treated, as well as the patient being treated. In general, in the case of oral or parenteral administration to adult humans weighing approximately 70 kg, a daily dosage of about 0.1 mg to about 5,000 mg, 1 mg to about 1,000 mg, or Img to 100 mg may be appropriate, although the lower and upper limits may be exceeded when indicated. The daily dosage can be administered as a single dose or in divided doses, or for parenteral administration, it may be given as continuous infusion.

[0139] In some embodiments, the term “a therapeutically effective amount” of a compound means an amount of compound that is effective to alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is within the skill in the art. The therapeutically effective amount or dosage of a compound according to this disclosure can vary within wide limits and may be determined in a manner known in the art. Such dosage will be adjusted to the individual requirements in each particular case including the specific compound(s) being administered, the route of administration, the condition being treated, as well as the patient being treated. In general, in the case of oral or parenteral administration to adult humans weighing approximately 70 kg, a daily dosage of about 0.1 mg to about 5,000 mg, 1 mg to about 1,000 mg, or 1 mg to 100 mg may be appropriate, although the lower and upper limits may be exceeded when indicated. The daily dosage can be administered as a single dose or in divided doses, or for parenteral administration, it may be given as continuous infusion.

[0140] In embodiments herein, a therapeutically effective amount of a compound may be an amount of compound that is effective to alleviate or ameliorate a condition or disease, or symptoms thereof, or prolong the survival of the subject being treated.

[0141] The term “pharmaceutically acceptable carrier” is intended to include any and all material compatible with pharmaceutical administration including solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and other materials and compounds compatible with pharmaceutical administration. Except insofar as any conventional media or agent is incompatible with a compound of the disclosure, use thereof in the compositions of the disclosure is contemplated. Supplementary active compounds can also be incorporated into the compositions.

COMPOUNDS

[0142] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-AB) is provided: or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

L’ is selected from the group consisting of *-N(R ¹ )-L-** and , wherein * denotes the point of attachment to Z, and ** denotes the point of attachment to R ¹ is H or C _1-6 alkyl;

X ¹ is N or CR ^s , wherein R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e ; wherein each of R ^d , R ^e and R ^f are independently H, C _1-6 alkyl, or C _3-20 cycloalkyl, wherein each of C _1-6 alkyl and C _3-20 cycloalkyl are independently optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -OR ^f1 , -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^fl is -C(O)CH ₂ NR ^d R ^e , -C(O)C _{1- 6} alkyl , -P(O)(OH) ₂ ; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _{1- 6} alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, 3 to 6 membered heterocyclyl, C _{3- 6} cycloalkyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH, C _1-6 alkoxyl, halo, oxo, -S(O) ₂ CH ₃ , or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N, CH, or CD, provided that: 1) only one of X ¹ , X ² , X ³ , and X ⁴ is N; or 2) X ¹ is N, X ² is CH, X ³ is CH, and X ⁴ is N; or 3) X ¹ is CR ^s and X ² , X ³ , and X ⁴ are each independently CH or CD;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo; Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _1-6 alkynyl optionally substituted with -OH; or R ^x is cyclobutenyl, dihydrofuranyl, bicyclobutanyl, or cyclopentenyl; or

Z is S(O) ₂ R ^x1 , wherein R ^x1 is C _2-6 alkenyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each 1; or n and m are each 2.

[0143] Any embodiments, aspects, variations, described herein with respect to one formula, may, where applicable, be applied to any other formula listed herein. For example, any embodiments, aspects, variations, described herein with respect to any one or more of formula (AB), (A), (B), (A’), (B’), (I-A), and (I-B) apply to formula (I-AB), the same as if each and every embodiments, aspects, and variations is specifically and individually listed with respect to formula (I-AB). It is understood that such embodiments apply to structural features of compounds, as well as methods of making and using such compounds. For example, it is understood that methods of using any one or more of formula (AB), (A), (B), (A’), (B’), (I-A), and (I-B), where applicable, apply to methods of using compounds of formula (I-AB), the same as if each and every embodiments, aspects, and variations is specifically and individually listed with respect to formula (I-AB).

[0144] In some embodiments, in conjunction with embodiments above or below, L’ of formula (I-AB) is *-N(R ¹ )-L-**. In some embodiments, in conjunction with embodiments above or below, L’ of formula (I-AB) is

[0145] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (AB) is provided: wherein: L’ is selected from the group consisting of *-N(R ¹ )-L-** and , wherein * denotes the point of attachment to Z, and ** denotes the point of attachment to

R ¹ is H or C _1-6 alkyl;

X ¹ is N or CR ^s , wherein R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e ; wherein each of R ^d , R ^e and R ^f are independently H, C _1-6 alkyl, or C _3-20 cycloalkyl, wherein each of C _1-6 alkyl and C _3-20 cycloalkyl are independently optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or-CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl;

X ² , X ³ , and X ⁴ are each independently N, CH, or CD, provided that only one of X ¹ , X ² , X ³ , and X ⁴ isN;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _1-6 alkynyl optionally substituted with -OH; or R ^x is cyclobutenyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each 1; or n and m are each 2.

[0146] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A) or (B) is provided: wherein:

R ¹ is H or C _1-6 alkyl;

X ¹ is N or CR ^s , wherein R ^s is selected from H, -CN, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, C _1-15 alkoxy, -NR ^d COR ^e , - CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, -OH, - CN, and C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N or CH, provided that only one of X ¹ , X ² , X ³ , and X ⁴ is N;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo; Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl and halo; or wherein R ^x is C _1-6 alkyl, optionally substituted with one or more halo;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each independently 1 or 2.

[0147] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A) or (B) is provided: wherein:

R ¹ is H or C _1-6 alkyl;

X ¹ is N or CR ^s , wherein R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e ; wherein each of R ^d , R ^e and R ^f are independently H, C _1-6 alkyl, or C _3-20 cycloalkyl, wherein each of C _1-6 alkyl and C _3-20 cycloalkyl are independently optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or-CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl;

X ² , X ³ , and X ⁴ are each independently N, CH, or CD, provided that only one of X ¹ , X ² , X ³ , and X ⁴ isN;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _1-6 alkynyl optionally substituted with -OH; or R ^x is cyclobutenyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each 1; or n and m are each 2.

[0148] In some embodiments, the compound is a compound of formula (A). In some embodiments, the compound is a compound of formula (B). [0149] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A’) or (B’) is provided: wherein:

X ¹ is N or CR ^s , wherein R ^s is selected from H, -CN, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, C _1-15 alkoxy, -NR ^d COR ^e , - CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, -OH, - CN, and C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N or CH, provided that only one of X ¹ , X ² , X ³ , and X ⁴ is N; B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl and halo; or wherein R ^x is C _1-6 alkyl, optionally substituted with one or more halo;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each independently 1 or 2.

[0150] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L’ is *-N(R ¹ )-L-**, wherein * denotes the point of attachment to Z, and ** denotes the point of attachment to

[0151] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L’ is , wherein * denotes the point of attachment to Z, and ** denotes the point of attachment [0152] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ¹ is H. In some embodiments, R ¹ is C _1-6 alkyl. In some embodiments, R ¹ is methyl.

[0153] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N. In some embodiments, X ¹ is C-CR ^s . In some embodiments, X ¹ is C-CR ^s , and R ^s is independently H, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -CN, C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , or -NR ^d R ^e . In other embodiments, R ^s is H. In other embodiments, each R ^s is halo. In other embodiments, R ^s is C _1-15 alkyl. In other embodiments, R ^s is C _6-20 aryl. In other embodiments, R ^s is 5 to 15 membered heteroaryl. In other embodiments, R ^s is C _3-20 cycloalkyl. In other embodiments, R ^s is 3 to 15 membered heterocyclyl. In other embodiments, R ^s is -OH. In other embodiments, R ^s is -CN. In other embodiments, R ^s is C _1-15 alkoxy. In other embodiments, R ^s is - NR ^d COR ^e . In other embodiments, R ^s is -CONR ^d R ^e . In other embodiments, R ^s is -SO ₂ R ^d . In other embodiments, R ^s is -SO ₂ NR ^d R ^e . In other embodiments, R ^s is -NR ^d SO ₂ R ^e . In other embodiments, R ^s is -NR ^d R ^e .

[0154] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _1-15 alkyl or C _1-15 alkoxy, the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e .

[0155] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _1-15 alkyl or C _1-15 alkoxy, the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, halo, oxo, -OH, -CN, -NR ^d R ^e , or 3 to 15 membered heterocyclyl optionally substituted with -OH. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is 3 to 15 membered heterocyclyl optionally substituted with -OH.

[0156] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl, the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 5 to 15 membered heteroaryl and R ^t2 is -OH. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _{3- 20} cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e .

[0157] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein each R ^s is independently further substituted by R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e , R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^d is H. In some embodiments, R ^d is C _1-6 alkyl. In some embodiments, R ^e is H. In some embodiments, R ^e is C _1-6 alkyl. In some embodiments, wherein R ^d is C _1-6 alkyl, the C _1-6 alkyl of R ^d is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -CN. In some embodiments, wherein R ^e is C _1-6 alkyl, the C _1-6 alkyl of R ^e is optionally substituted with one or more halo, oxo, - OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -CN.

[0158] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl or 5 to 6 membered heteroaryl. In some embodiments, B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In some embodiments, the phenyl or 5 to 6 membered heteroaryl of B is each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-15 alkyl. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _{1- 15} alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _{1- 15} alkyl. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, wherein B is phenyl or 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is C _1-15 alkyl, or C _1-6 alkoxy, the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, the C _1-15 alkyl of R ^t is substituted by one or more fluoro. In some embodiments, the C _1-15 alkoxy of R ^t is substituted by one or more fluoro. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo.

[0159] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In other embodiments, B is unsubstituted phenyl. In other embodiments, B is substituted phenyl. In other embodiments, B is phenyl substituted by one or more R ^t In other embodiments, R ^t is C _1-6 alkoxy. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more halo. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more fluoro. In other embodiments, B is

[0160] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N or C-CR ^s . In some embodiments, X ¹ is N. In some embodiments, X ¹ is C-CR ^s .

[0161] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is unsubstituted C _1-15 alkyl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is

N; and R ^s is

[0162] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is methylene, optionally substituted with one or more C _1-6 alkyl. In some embodiments, L is unsubstituted methylene. In some embodiments, L is is methylene substituted with one or more C _1-6 alkyl.

[0163] In some embodiments, provided herein is a compound of formula (A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _{1- 6} alkyl and halo; or wherein R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl and halo. In some embodiments, R ^x is unsubstituted C _2-6 alkenyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more C _1-6 alkyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more halo. In some embodiments, R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is unsubstituted C _{1- 6} alkyl. In some embodiments, R ^x is C _1-6 alkyl substituted with one or more halo.

[0164] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _{1- 6} alkyl and halo; or wherein R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl and halo. In some embodiments, R ^x is unsubstituted C _2-6 alkenyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more C _1-6 alkyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more halo. In some embodiments, R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is unsubstituted C _{1- 6} alkyl. In some embodiments, R ^x is C _1-6 alkyl substituted with one or more halo.

[0165] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein X ¹ is N or CR ^s , wherein R ^s is selected from H, -CN and C _1-15 alkyl optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is, at each occurrence, -OH; X ² and X ³ are each CH, and X ⁴ is N or CH; B is phenyl optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from C _1-6 alkoxy optionally substituted with one or more halo, and S(R ^y ) ₅ , wherein each R ^y is halo; L is methylene; and Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, or wherein R ^x is C _1-6 alkyl substituted with halo.

[0166] In some embodiments, X ¹ is N and X ² , X ³ andX ⁴ are each CH. In embodiments, X ¹ is CR ^s and X ² , X ³ and X ⁴ are each CH. In some embodiments, X ¹ is CR ^s , wherein R ^s is H; X ² and X ³ are each CH andX ⁴ is N. In some embodiments, X ¹ is CR ^s and R ^s is methyl substituted with one R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, X ¹ is CR ^s and R ^s is ethyl substituted with two R ^t ₁ , wherein R ^t ₁ is, at each occurrence, -OH. In some embodiments, B is phenyl substituted with one R ^t , wherein R ^t is S(R ^y ) ₅ , wherein each R ^y is fluoro. In some embodiments, B is phenyl substituted with one R ^t , wherein R ^t is trifluoromethoxy. In some embodiments, Z is - C(O)R ^x , wherein R ^x is ethenyl. In some embodiments, Z is -C(O)R ^x , wherein R ^x is ethyl substituted with chloro.

[0167] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N. In some embodiments, X ¹ is C-CR ^s . In some embodiments, X ¹ is C-CR ^s and C-CR ^s , and R ^s is independently H, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -CN, C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , or -NR ^d R ^e . In other embodiments, R ^s is H. In other embodiments, each R ^s is halo. In other embodiments, R ^s is C _1-15 alkyl. In other embodiments, R ^s is C _6-20 aryl. In other embodiments, R ^s is 5 to 15 membered heteroaryl. In other embodiments, R ^s is C _3-20 cycloalkyl. In other embodiments, R ^s is 3 to 15 membered heterocyclyl. In other embodiments, R ^s is -OH. In other embodiments, R ^s is -CN. In other embodiments, R ^s is C _1-15 alkoxy. In other embodiments, R ^s is -NR ^d COR ^e . In other embodiments, R ^s is -CONR ^d R ^e . In other embodiments, R ^s is -SO ₂ R ^d . In other embodiments, R ^s is -SO ₂ NR ^d R ^e . In other embodiments, R ^s is -NR ^d SO ₂ R ^e . In other embodiments, R ^s is -NR ^d R ^e .

[0168] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _1-15 alkyl or C _1-15 alkoxy, the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e .

[0169] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl, the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 5 to 15 membered heteroaryl and R ^t2 is -OH. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _{3- 20} cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e .

[0170] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein each R ^s is independently further substituted by R ^t2 , wherein R ^t2 is -NR ^d R ^e , R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^d is H. In some embodiments, R ^d is C _1-6 alkyl. In some embodiments, R ^e is H. In some embodiments, R ^e is C _1-6 alkyl. In some embodiments, wherein R ^d is C _1-6 alkyl, the C _1-6 alkyl of R ^d is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -CN. In some embodiments, wherein R ^e is C _1-6 alkyl, the C _1-6 alkyl of R ^e is optionally substituted with one or more halo, oxo, - OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -CN.

[0171] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl or 5 to 6 membered heteroaryl. In some embodiments, B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In some embodiments, the phenyl or 5 to 6 membered heteroaryl of B is each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-15 alkyl. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _{1- 15} alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _{1- 15} alkyl. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, wherein B is phenyl or 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is C _1-15 alkyl, or C _1-6 alkoxy, the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, the C _1-15 alkyl of R ^t is substituted by one or more fluoro. In some embodiments, the C _1-15 alkoxy of R ^t is substituted by one or more fluoro. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo.

[0172] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In other embodiments, B is unsubstituted phenyl. In other embodiments, B is substituted phenyl. In other embodiments, B is phenyl substituted by one or more R ^t In other embodiments, R ^t is C _1-6 alkoxy. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more halo. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more fluoro. In other embodiments, B is

[0173] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n and m are each independently 1 or 2. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, n is 1 and m is 1. In some embodiments, n is 1 and m is 2. In some embodiments, n is 2 and m is 1. In some embodiments, n is 2 and m is 2.

[0174] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N or C-CR ^s . In some embodiments, X ¹ is N. In some embodiments, X ¹ is C-CR ^s .

[0175] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-R ^s , X ² is C- H, X ³ is C-H, X ⁴ is N; and R ^s is unsubstituted C _1-15 alkyl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is

N; and R ^s is

[0176] In some embodiments, in conjunction with embodiments above or below, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable OH salt thereof, wherein X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is

[0177] In some embodiments, provided herein is a compound of formula (B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _{1- 6} alkyl and halo; or wherein R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl and halo. In some embodiments, R ^x is unsubstituted C _2-6 alkenyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more C _1-6 alkyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more halo. In some embodiments, R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is unsubstituted C _{1- 6} alkyl. In some embodiments, R ^x is C _1-6 alkyl substituted with one or more halo.

[0178] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A) or (I-B) is provided: or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein: X ¹ is N or CR ^s , wherein R ^s is selected from H, -CN, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, C _1-15 alkoxy, -NR ^d COR ^e , - CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN and -NR ^d R ^e , wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, -OH, - CN, and C _1-6 alkyl;

X ² , X ³ , andX ⁴ are each independently N or CH, provided that only one of X ¹ , X ² , X ³ , and X ⁴ is N;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

R ^a , R ^b , and R ^c are each independently H, halo, or C _1-5 alkyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each independently 1 or 2.

[0179] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N. In some embodiments, X ¹ is C-CR ^s . In some embodiments, X ¹ is C-CR ^s , and R ^s is independently H, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -CN, C _1-15 alkoxy, or -NR ^d R ^e . In other embodiments, R ^s is H. In other embodiments, each R ^s is halo. In other embodiments, R ^s is C _1-15 alkyl. In other embodiments, R ^s is C _6-20 aryl. In other embodiments, R ^s is 5 to 15 membered heteroaryl. In other embodiments, R ^s is C _3-20 cycloalkyl. In other embodiments, R ^s is 3 to 15 membered heterocyclyl. In other embodiments, R ^s is -OH. In other embodiments, R ^s is -CN. In other embodiments, R ^s is C _{1- 15} alkoxy. In other embodiments, R ^s is -NR ^d R ^e .

[0180] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _1-15 alkyl or C _1-15 alkoxy, the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e .

[0181] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl, the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 5 to 15 membered heteroaryl and R ^t2 is -OH. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _{3- 20} cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e .

[0182] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein each R ^s is independently further substituted by R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e , R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^d is H. In some embodiments, R ^d is C _1-6 alkyl. In some embodiments, R ^e is H. In some embodiments, R ^e is C _1-6 alkyl. In some embodiments, wherein R ^d is C _1-6 alkyl, the C _1-6 alkyl of R ^d is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -CN. In some embodiments, wherein R ^e is C _1-6 alkyl, the C _1-6 alkyl of R ^e is optionally substituted with one or more halo, oxo, - OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -CN. [0183] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl or 5 to 6 membered heteroaryl. In some embodiments, B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In some embodiments, the phenyl or 5 to 6 membered heteroaryl of B is each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-15 alkyl. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _{1- 15} alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _{1- 15} alkyl. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, wherein B is phenyl or 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is C _1-15 alkyl, or C _1-6 alkoxy, the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, the C _1-15 alkyl of R ^t is substituted by one or more fluoro. In some embodiments, the C _1-15 alkoxy of R ^t is substituted by one or more fluoro. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo.

[0184] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In other embodiments, B is unsubstituted phenyl. In other embodiments, B is substituted phenyl. In other embodiments, B is phenyl substituted by one or more R ^t In other embodiments, R ^t is C _1-6 alkoxy. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more halo. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more fluoro. In other embodiments, B is [0185] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ^a , R ^b , and R ^c are each independently H, halo, or C _1-5 alkyl. In some embodiments, R ^a is H. In some embodiments, R ^a is halo. In some embodiments, R ^a is C _1-5 alkyl. In some embodiments, R ^b is H. In some embodiments, R ^b is halo. In some embodiments, R ^b is C _1-5 alkyl. In some embodiments, R ^c is H. In some embodiments, R ^c is halo. In some embodiments, R ^c is C _1-5 alkyl. In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ^a , R ^b , and R ^c are H.

[0186] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N or C-CR ^s . In some embodiments, X ¹ is N. In some embodiments, X ¹ is C-CR ^s .

[0187] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-R ^s , X ² is C- H, X ³ is C-H, X ⁴ is N; and R ^s is unsubstituted C _1-15 alkyl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is

OH

HO.

N; and R ^s is

[0188] In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is methylene, optionally substituted with one or more C _1-6 alkyl. In some embodiments, L is unsubstituted methylene. In some embodiments, L is is methylene substituted with one or more C _1-6 alkyl.

[0189] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N. In some embodiments, X ¹ is C-CR ^s . In some embodiments, X ¹ is C-CR ^s and C-CR ^s , and R ^s is independently H, halo, C _1-15 alkyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -CN, C _1-15 alkoxy, or -NR ^d R ^e . In other embodiments, R ^s is H. In other embodiments, each R ^s is halo. In other embodiments, R ^s is C _1-15 alkyl. In other embodiments, R ^s is C _6-20 aryl. In other embodiments, R ^s is 5 to 15 membered heteroaryl. In other embodiments, R ^s is C _3-20 cycloalkyl. In other embodiments, R ^s is 3 to 15 membered heterocyclyl. In other embodiments, R ^s is -OH. In other embodiments, R ^s is -CN. In other embodiments, R ^s is C _1-15 alkoxy. In other embodiments, R ^s is -NR ^d R ^e . [0190] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _1-15 alkyl or C _1-15 alkoxy, the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e .

[0191] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein R ^s is C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl, the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, halo, oxo, -OH, -CN, or -NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 5 to 15 membered heteroaryl and R ^t2 is -OH. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _{3- 20} cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e .

[0192] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-CR ^s , and wherein each R ^s is independently further substituted by R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e , R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^d is H. In some embodiments, R ^d is C _1-6 alkyl. In some embodiments, R ^e is H. In some embodiments, R ^e is C _1-6 alkyl. In some embodiments, wherein R ^d is C _1-6 alkyl, the C _1-6 alkyl of R ^d is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -CN. In some embodiments, wherein R ^e is C _1-6 alkyl, the C _1-6 alkyl of R ^e is optionally substituted with one or more halo, oxo, - OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -CN.

[0193] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl or 5 to 6 membered heteroaryl. In some embodiments, B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In some embodiments, the phenyl or 5 to 6 membered heteroaryl of B is each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-15 alkyl. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _{1- 15} alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _{1- 15} alkyl. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, wherein B is phenyl or 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is C _1-15 alkyl, or C _1-6 alkoxy, the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, the C _1-15 alkyl of R ^t is substituted by one or more fluoro. In some embodiments, the C _1-15 alkoxy of R ^t is substituted by one or more fluoro. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo.

[0194] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In other embodiments, B is unsubstituted phenyl. In other embodiments, B is substituted phenyl. In other embodiments, B is phenyl substituted by one or more R ^t In other embodiments, R ^t is C _1-6 alkoxy. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more halo. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more fluoro. In other embodiments, B is

[0195] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ^a , R ^b , and R ^c are each independently H, halo, or C _1-5 alkyl. In some embodiments, R ^a is H. In some embodiments, R ^a is halo. In some embodiments, R ^a is C _1-5 alkyl. In some embodiments, R ^b is H. In some embodiments, R ^b is halo. In some embodiments, R ^b is C _1-5 alkyl. In some embodiments, R ^c is H. In some embodiments, R ^c is halo. In some embodiments, R ^c is C _1-5 alkyl. In some embodiments, provided herein is a compound of formula (I-A), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ^a , R ^b , and R ^c are H. [0196] In some embodiments, in conjunction with embodiments above or below, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ^b and R ^c are each H, and R ^a is halo.

[0197] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n and m are each independently 1 or 2. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, n is 1 and m is 1. In some embodiments, n is 1 and m is 2. In some embodiments, n is 2 and m is 1. In some embodiments, n is 2 and m is 2.

[0198] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N or C-CR ^s . In some embodiments, X ¹ is N. In some embodiments, X ¹ is C-CR ^s .

[0199] In some embodiments, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-R ^s , X ² is C- H, X ³ is C-H, X ⁴ is N; and R ^s is unsubstituted C _1-15 alkyl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is

N; and R ^s is

[0200] In some embodiments, in conjunction with embodiments above or below, provided herein is a compound of formula (I-B), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is

[0201] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A’) or (B’) is provided: wherein:

X ¹ is N or CR ^s , wherein R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e ; wherein each of R ^d , R ^e and R ^f are independently H, C _1-6 alkyl, or C _3-20 cycloalkyl, wherein each of C _1-6 alkyl and C _3-20 cycloalkyl are independently optionally substituted with one or more halo, oxo, -OH, or -CN; wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or-CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl;

X ² , X ³ , and X ⁴ are each independently N, CH, or CD, provided that only one of X ¹ , X ² , X ³ , and X ⁴ isN;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _1-6 alkynyl optionally substituted with -OH; or R ^x is cyclobutenyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each 1; or n and m are each 2.

[0202] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A) or (I-B) is provided: or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

X ¹ is N or CR ^s , wherein R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e ; wherein each of R ^d , R ^e and R ^f are independently H, C _1-6 alkyl, or C _3-20 cycloalkyl, wherein each of C _1-6 alkyl and C _3-20 cycloalkyl are independently optionally substituted with one or more halo, oxo, -OH, or -CN wherein the C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or-CN; and wherein the C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl;

X ² , X ³ , and X ⁴ are each independently N, CH, or CD, provided that only one of X ¹ , X ² , X ³ , and X ⁴ isN;

B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence selected from halo, C _1-15 alkyl, C _1-6 alkoxy, and S(R ^y ) ₅ , wherein each R ^y is halo, and wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo;

R ^a , R ^b , and R ^c are each independently H, halo, or C _1-5 alkyl;

L is methylene, optionally substituted with one or more C _1-6 alkyl; and n and m are each 1; or n and m are each 2.

[0203] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N. In some embodiments, X ¹ is CR ^s . In some embodiments, X ¹ is CR ^s , and R ^s is independently R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _1-6 alkynyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _{3- 20} cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , - SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e . In other embodiments, each R ^s is H. In other embodiments, each R ^s is D. In other embodiments, each R ^s is -CN. In other embodiments, each R ^s is halo. In other embodiments, each R ^s is C _1-15 alkyl. In other embodiments, each R ^s is C _{1- 6} alkynyl. In other embodiments, each R ^s is C _6-20 aryl. In other embodiments, each R ^s is 5 to 15 membered heteroaryl. In other embodiments, each R ^s is C _3-20 cycloalkyl. In other embodiments, each R ^s is 3 to 15 membered heterocyclyl. In other embodiments, each R ^s is -OH. In other embodiments, each R ^s is -OR ^f . In other embodiments, each R ^s is C _1-15 alkoxy. In other embodiments, each R ^s is -NR ^d COR ^e . In other embodiments, each R ^s is -CONR ^d R ^e . In other embodiments, each R ^s is -SO ₂ R ^d . In other embodiments, each R ^s is -SO ₂ NR ^d R ^e . In other embodiments, each R ^s is -NR ^d SO ₂ R ^e . In other embodiments, each R ^s is -NR ^d R ^e .

[0204] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , and wherein R ^s is C _{1- 15} alkyl or C _1-15 alkoxy, C _1-15 alkyl and C _1-15 alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _{1- 15} alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _{1- 15} alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _{1- 15} alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _{1- 15} alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is 3 to 15 membered heterocyclyl optionally substituted with one or more -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is 3 to 15 membered heterocyclyl optionally substituted with one or more -OH.

[0205] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , and wherein R ^s is C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, or 3 to 15 membered heterocyclyl, the C _{6- 20} aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _{1- 6} alkoxyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more - OH or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _{1- 6} alkyl.

[0206] In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkoxyl. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl.

[0207] In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkoxyl. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl.

[0208] In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkoxyl. In some embodiments, R ^s is C _{3- 20} cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl.

[0209] In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R' is C _1-6 alkoxyl. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl.

[0210] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , and wherein each R ^s is independently further substituted by R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e , R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^d is H. In some embodiments, R ^d is C _{1- 6} alkyl. In some embodiments, R ^e is H. In some embodiments, R ^e is C _1-6 alkyl. In some embodiments, wherein R ^d is C _1-6 alkyl, the C _1-6 alkyl of R ^d is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -CN. In some embodiments, wherein R ^e is C _1-6 alkyl, the C _1-6 alkyl of R ^e is optionally substituted with one or more halo, oxo, - OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -CN.

[0211] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl or 5 to 6 membered heteroaryl. In some embodiments, B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In some embodiments, the phenyl or 5 to 6 membered heteroaryl of B is each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-15 alkyl. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _1-15 alkyl. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, wherein B is phenyl or 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is C _1-15 alkyl, or C _1-6 alkoxy, the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, the C _1-15 alkyl of R ^t is substituted by one or more fluoro. In some embodiments, the C _1-15 alkoxy of R ^t is substituted by one or more fluoro. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo.

[0212] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In other embodiments, B is unsubstituted phenyl. In other embodiments, B is substituted phenyl. In other embodiments, B is phenyl substituted by one or more R ^t . In other embodiments, R ^t is C _1-6 alkoxy. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more halo. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more fluoro. In other embodiments, B is [0213] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N or CR ^s . In some embodiments, X ¹ is N. In some embodiments, X ¹ is CR ^s .

[0214] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (I-A), (B), (B’), or (I-B), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is unsubstituted C _1-15 alkyl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is

. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments,

X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s ,

X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H,

X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-

H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments,

X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X is C-R ^s ,

X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is

N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is In other embodiments,

X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is

C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is

C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments,

X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s ,

X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is

C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is

N; and R ^s is methyl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments,

X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s ,

X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is

N; and R ^s is Cl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is

In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments,

X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is methylene, optionally substituted with one or more C _{1- 6} alkyl. In some embodiments, L is unsubstituted methylene. In some embodiments, L is is methylene substituted with one or more C _1-6 alkyl.

[0215] In some embodiments, provided herein is a compound of formula (AB), (A), (A’), (B), or (B’), or any applicable subformulae thereof,, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _{1- 6} alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _{1- 6} alkoxyl optionally substituted with -OH; or R ^x is cyclobutenyl. In some embodiments, R ^x is C _{2- 6} alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo. In some embodiments, R ^x is unsubstituted C _2-6 alkenyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more C _1-6 alkyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more deuterium. In some embodiments, R ^x is C _{2- 6} alkenyl substituted with one or more -OH. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more C _1-6 alkoxyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more halo. In some embodiments, R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is unsubstituted C _1-6 alkyl. In some embodiments, R ^x is C _1-6 alkyl substituted with one or more halo. In some embodiments, R ^x is C _1-6 alkynyl optionally substituted with -OH. In some embodiments, R ^x is unsubstituted C _1-6 alkynyl. In some embodiments, R ^x is C _1-6 alkynyl substituted with one or more -OH. In some embodiments, R ^x is or R ^x is cyclobutenyl. [0216] In some embodiments, provided herein is a compound of formula (I- AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N. In some embodiments, X ¹ is CR ^s . In some embodiments, X ¹ is CR ^s and CR ^s , and R ^s is independently R ^s is selected from H, deuterium, -CN, halo, C _1-15 alkyl, C _{1- 6} alkoxyl, C _6-20 aryl, 5 to 15 membered heteroaryl, C _3-20 cycloalkyl, 3 to 15 membered heterocyclyl, -OH, -OR ^f , C _1-15 alkoxy, -NR ^d COR ^e , -CONR ^d R ^e , -SO ₂ R ^d , -SO ₂ NR ^d R ^e , -NR ^d SO ₂ R ^e , and -NR ^d R ^e . In other embodiments, each R ^s is H. In other embodiments, each R ^s is D. In other embodiments, each R ^s is -CN. In other embodiments, each R ^s is halo. In other embodiments, each R ^s is C _1-15 alkyl. In other embodiments, each R ^s is C _1-6 alkynyl. In other embodiments, each R ^s is C _6-20 aryl. In other embodiments, each R ^s is 5 to 15 membered heteroaryl. In other embodiments, each R ^s is C _3-20 cycloalkyl. In other embodiments, each R ^s is 3 to 15 membered heterocyclyl. In other embodiments, each R ^s is -OH. In other embodiments, each R ^s is -OR ^f . In other embodiments, each R ^s is C _1-15 alkoxy. In other embodiments, each R ^s is -NR ^d COR ^e . In other embodiments, each R ^s is -CONR ^d R ^e . In other embodiments, each R ^s is -SO ₂ R ^d . In other embodiments, each R ^s is -SO ₂ NR ^d R ^e . In other embodiments, each R ^s is -NR ^d SO ₂ R ^e . In other embodiments, each R ^s is -NR ^d R ^e .

[0217] In some embodiments, provided herein is a compound of formula (I- AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , and wherein R ^s is C _1-15 alkyl or C _1-15 alkoxy, C _1-15 alkyl and C _{1- 15} alkoxy of R ^s are each independently optionally substituted with one or more R ^t ₁ , wherein R ^t ₁ is independently, at each occurrence, selected from halo, oxo, -OH, -OR ^f1 , -CN, -NR ^d R ^e , and 3 to 15 membered heterocyclyl optionally substituted with one or more -OH; wherein R ^fl is - C(O)CH ₂ NR ^d R ^e , -C(O)C _1-6 alkyl, -P(O)(OH) ₂ ; wherein R ^d and R ^e are each independently H or C _{1- 6} alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OR ^fl , wherein R ^fl is -C(O)CH ₂ NR ^d R ^e , -C(O)C _1-6 alkyl, -P(O)(OH) ₂ . In some embodiments, R ^s is C _{1- 15} alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _{1- 15} alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _{1- 15} alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is 3 to 15 membered heterocyclyl optionally substituted with one or more -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is halo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is oxo. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is OR ^f1 , wherein R ^fl is -C(O)CH ₂ NR ^d R ^e , -C(O)C _1-6 alkyl, -P(O)(OH) ₂ . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -CN. In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e . In some embodiments, R ^s is C _1-15 alkoxy substituted with one or more R ^t ₁ , wherein R ^t ₁ is 3 to 15 membered heterocyclyl optionally substituted with one or more -OH.

[0218] In some embodiments, provided herein is a compound of formula (I-AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , and wherein R ^s is C _6-20 aryl, 5 to 15 membered heteroaryl, C _{3- 20} cycloalkyl, or 3 to 15 membered heterocyclyl, the C _6-20 aryl, 5 to 15 membered heteroaryl, C _{3- 20} cycloalkyl, and 3 to 15 membered heterocyclyl of R ^s are each independently optionally substituted with one or more R ^t2 , wherein R ^t2 is independently, at each occurrence, selected from halo, oxo, -OH, -CN, C(O)NH ₂ , -C(O)NR ^d R ^e , -NR ^d R ^e , C _1-6 alkoxyl, 3 to 6 membered heterocyclyl, C _3-6 cycloalkyl, and C _1-6 alkyl; wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH, C _1-6 alkoxyl, halo, oxo, -S(O) ₂ CH ₃ , or -NR ^d R ^e ; wherein R ^d and R ^e are each independently H, -C(O)CH ₃ , -C(O)C _1-6 alkyl, or C _1-6 alkyl.

[0219] In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkoxyl. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is 3 to 6 membered heterocyclyl. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is C _3- 6cycloalkyl. In some embodiments, R ^s is C _6-20 aryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl, wherein the C _1-6 alkyl of R ^t2 is optionally substituted with one or more -OH, C _1-6 alkoxyl, halo, oxo, -S(O) ₂ CH ₃ , or -NR ^d R ^e .

[0220] In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkoxyl. In some embodiments, R ^s is 5 to 15 membered heteroaryl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkoxyl. In some embodiments, R ^s is C _3-20 cycloalkyl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is halo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is oxo. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -OH. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -CN. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is C(O)NH ₂ . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -C(O)NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is -NR ^d R ^e . In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkoxyl. In some embodiments, R ^s is 3 to 15 membered heterocyclyl substituted with one or more R ^t2 , wherein R ^t2 is C _1-6 alkyl.

[0221] In some embodiments, provided herein is a compound of formula (I-AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , and wherein each R ^s is independently further substituted by R ^t ₁ , wherein R ^t ₁ is -NR ^d R ^e , R ^d and R ^e are each independently H or C _1-6 alkyl, and the C _1-6 alkyl of R ^d or R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, R ^d isH. In some embodiments, R ^d is C _1-6 alkyl. In some embodiments, R ^e is H. In some embodiments, R ^e is C _1-6 alkyl. In some embodiments, wherein R ^d is C _1-6 alkyl, the C _1-6 alkyl of R‘ is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^d is substituted with one or more - CN. In some embodiments, wherein R ^e is C _1-6 alkyl, the C _1-6 alkyl of R ^e is optionally substituted with one or more halo, oxo, -OH, or -CN. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more halo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more oxo. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -OH. In some embodiments, the C _1-6 alkyl of R ^e is substituted with one or more -CN.

[0222] In some embodiments, provided herein is a compound of formula (I-AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl or 5 to 6 membered heteroaryl. In some embodiments, B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In some embodiments, the phenyl or 5 to 6 membered heteroaryl of B is each independently optionally substituted with one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _{1- 15} alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _{1- 15} alkyl. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, B is phenyl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is independently at each occurrence halo, C _1-15 alkyl, or C _1-6 alkoxy, wherein the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is halo. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _{1- 15} alkyl. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is C _1-6 alkoxy. In some embodiments, wherein B is phenyl or 5 to 6 membered heteroaryl substituted by one or more R ^t , wherein R ^t is C _1-15 alkyl, or C _1-6 alkoxy, the C _1-15 alkyl or C _1-6 alkoxy of R ^t is optionally substituted with one or more halo. In some embodiments, the C _1-15 alkyl of R ^t is substituted by one or more fluoro. In some embodiments, the C _1-15 alkoxy of R ^t is substituted by one or more fluoro. In some embodiments, B is 5 to 6 membered heteroaryl substituted by one or more R ^t , and R ^t is S(R ^y ) ₅ , wherein each R ^y is halo.

[0223] In some embodiments, provided herein is a compound of formula (I-AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein B is phenyl. In some embodiments, B is 5 to 6 membered heteroaryl. In other embodiments, B is unsubstituted phenyl. In other embodiments, B is substituted phenyl. In other embodiments, B is phenyl substituted by one or more R ^t . In other embodiments, R ^t is C _{1- 6} alkoxy. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more halo. In other embodiments, R ^t is C _1-6 alkoxy substituted by one or more fluoro. In other embodiments, B is

[0224] In some embodiments, provided herein is a compound of formula (I-AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N or CR ^s , X ² , X ³ , and X ⁴ are each independently N, CH, or CD, provided that: 1) only one of X ¹ , X ² , X ³ , and X ⁴ is N; or 2) X ¹ is N, X ² is CH, X ³ is CH, and X ⁴ is N; or 3) X ¹ is CR ^s andX ² , X ³ , andX ⁴ are each independently CH or CD.

[0225] In some embodiments, X ¹ is N, X ² , X ³ , and X ⁴ are each independently CH or CD. In some embodiments, X ¹ is N, X ² and X ³ are each independently CH or CD, and X ⁴ is N. In some embodiments, X ¹ is CR ^s . In some embodiments, X ¹ is CR ^s and X ² is N. In some embodiments, X ¹ is CR ^s and X ³ is N. In some embodiments, X ¹ is CR ^s and X ⁴ is N.

[0226] In some embodiments, provided herein is a compound of formula (I-AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is unsubstituted C _1-15 alkyl. In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ . In other embodiments, X ¹ is C-R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is C _1-15 alkyl substituted with one or more R ^t ₁ , wherein R ^t ₁ is -OH. In other embodiments, X ¹ is C-

R ^s , X ² is C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In other embodiments, X ¹ is C-R ^s , X ² is

C-H, X ³ is C-H, X ⁴ is N; and R ^s is . In some embodiments, in conjunction with embodiments above or below, R ^s is selected from the group consisting of methyl, cyano, halo, chloro, -H, -CCH,

[0227] In some embodiments, provided herein is a compound of formula (I-AB) or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is methylene, optionally substituted with one or more C _1-6 alkyl. In some embodiments, L is unsubstituted methylene. In some embodiments, L is is methylene substituted with one or more C _1-6 alkyl.

[0228] In some embodiments, provided herein is a compound of formula (I-AB), or any applicable subformulae thereof, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo; or R ^x is C _1-6 alkyl, optionally substituted with one or more halo; or R ^x is C _1-6 alkynyl optionally substituted with - OH; or R ^x is cyclobutenyl, dihydrofuranyl, bicyclobutanyl, or cyclopentenyl. In some embodiments, R ^x is C _2-6 alkenyl, optionally substituted with one or more substituents selected from C _1-6 alkyl, deuterium, -OH, C _1-6 alkoxyl, and halo. In some embodiments, R ^x is unsubstituted C _2-6 alkenyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more C _1-6 alkyl. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more deuterium. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more -OH. In some embodiments, R ^x is C _2-6 alkenyl substituted with one or more C _1-6 alkoxyl. In some embodiments, R ^x is C _{2- 6} alkenyl substituted with one or more halo. In some embodiments, R ^x is C _1-6 alkyl, optionally substituted with one or more halo. In some embodiments, R ^x is unsubstituted C _1-6 alkyl. In some embodiments, R ^x is C _1-6 alkyl substituted with one or more halo. In some embodiments, R ^x is C _{1- 6} alkoxyl optionally substituted with -OH. In some embodiments, R ^x is unsubstituted C _1-6 alkynyl. In some embodiments, R ^x is C _1-6 alkynyl substituted with one or more -OH. In some embodiments, R ^x is cyclobutenyl. In some embodiments, R ^x is dihydrofuranyl. In some embodiments, R ^x is bicyclobutanyl. In some embodiments, R ^x is cyclopentenyl. In some embodiments, Z is S(O) ₂ R ^x1 , wherein R ^x1 is C _2-6 alkenyl. [0229] In some embodiments, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (AB’) is provided: wherein X ² , X ³ , X ⁴ , R ^s , B, L’, and Z are as defined in formula (AB). It is understood that embodiments of X ² , X ³ , X ⁴ , R ^s , B, L’, and Z described for formula (AB) may, where applicable, apply in some embodiments to formula (AB’). In some embodiments, R ^s is not H or deuterium.

In some embodiments, R ^s is selected from the group consisting of methyl, cyano, halo, chloro, -H,

and . In some embodiments, R ^s is C _1-6 alkyl substituted with one or more -OH. In some embodiments, R ^s is C _1-

3 alkyl substituted with one or more -OH. In some embodiments, R ^s is , or a stereoisomer thereof. In some embodiments, R ^s is

[0230] In some embodiments, compounds of any one of the formulae described herein, may comprise one or more of the following structural features: i) L’ is *-NH-CH ₂ -**; or ii) L’ is and/or iii) B is phenyl substituted with haloC _1-6 alkoxy; and/or iv) R ^s is C _1-6 alkyl substituted with one or more -OH; and/or v) X ² is CH; and/or vi) X ³ is CH; and/or vii) X ⁴ is N; and/or viii) Z is -C(O)R ^x , wherein R ^x is unsubstituted C _2-6 alkenyl; and/or ix) Z is -C(O)R ^x , wherein R ^x is C _2-6 alkenyl optionally substituted with one or more halo. In some embodiments, compounds of any one of the formulae described herein, may comprise two of the structural features described above, such as i) and iii), i) and iv), i) and v), i) and vi), i) and vii), i) and viii), i) and (ix), ii) and iii), ii) and iv), ii) and v), ii) and vi), ii) and vii), ii) and viii), ii) and (ix), iii) and iv), iii) and v), iii) and vi), iii) and vii), iii) and viii), iii) and ix), iv) and v), iv) and vi), iv) and vii), iv) and viii), iv and ix), v) and vi), v) and vii), v) and viii), v) and ix), vi) and vii), vi) and viii), vi) and ix), vii) and viii), and vii) and ix). In some embodiments, compounds of any one of the formulae described herein, may comprise three of the structural features described above, such as i) and (iii) and iv), i) and (iii) and v), i) and iii) and vi), i) and (iii) and vii), i) and iii) and viii), i) and iii) and (ix), ii) and iii) and iv), ii) and iii) and v), ii) and iii) and vi), ii) and iii) and vii), ii) and iii) and viii), ii) and iii) and (ix), iii) and iv) and v), iii) and iv) and vi), iii) and iv) and vii), iii) and iv) and viii), iii) and iv) and ix), iv) and v) and vi), iv) and v) and vii), iv) and v) and viii), iv) and v) and ix), v) and vi) and vii), v) and vi) and viii), v) and vi) and ix), vi) and vii) and viii), and vi) and vii) and ix). In some embodiments, compounds of any one of the formulae described herein, may comprise four of the structural features described above, such as i) and iii) and iv) and v), i) and iii) and iv) and vi), i) and (iii) and iv) and vii), i) and iii) and iv) and viii), i) and iii) and iv) and (ix), ii) and iii) and iv) and v), ii) and iii) and iv) and vi), ii) and iii) and iv) and vii), ii) and iii) and iv) and viii), ii) and iii) and iv) and (ix), iii) and iv) and v) and vi), iii) and iv) and v) and vii), iii) and iv) and v) and viii), iii) and iv) and v) and ix), iv) and v) and vi) and vii), iv) and v) and vi) and viii), iv) and v) and vi) and ix), v) and vi) and vii) and viii), and v) and vi) and vii) and ix). In some embodiments, compounds of any one of the formulae described herein, may comprise five of the structural features described above, such as i) and iii) and iv) and v) and vi), i) and iii) and iv) and v) and vii), i) and iii) and iv) and v) and viii), i) and iii) and iv) and v) and ix), ii) and iii) and iv) and v) and vi), ii) and iii) and iv) and v) and vii), ii) and iii) and iv) and v) and viii), ii) and iii) and iv) and v) and ix), iii) and iv) and v) and vi) and vii), iii) and iv) and v) and viii), iii) and iv) and v) and ix), iv) and v) and vi) and vii) and viii), and iv) and v) and vi) and vii) and ix). In some embodiments, compounds of any one of the formulae described herein, may comprise six of the structural features described above, such as i) and iii) and iv) and v) and vi) and vii), i) and iii) and iv) and v) and vi) and viii), i) and iii) and iv) and v) and vi) and ix), ii) and iii) and iv) and v) and vi) and vii), ii) and iii) and iv) and v) and vi) and viii), ii) and iii) and iv) and v) and vi) and ix), iii) and iv) and v) and vi) and vii) and viii), and iii) and iv) and v) and vi) and vii) and ix). In some embodiments, compounds of any one of the formulae described herein, may comprise seven of the structural features described above, such as i) and iii) and iv) and v) and vi) and vii) and viii), i) and iii) and iv) and v) and vi) and vii) and ix), ii) and iii) and iv) and v) and vi) and vii) and viii), and ii) and iii) and iv) and v) and vi) and vii) and ix). [0231] In some embodiments, in conjunction with embodiments above or below, reference to “one or more” may be 1 to 5, 1 to 4, 1 to 3, 1 to 2, 5, 4, 3, 2, or 1.

[0232] In some embodiments, in conjunction with embodiments above or below, reference to “one or more substituents”, for example, “one or more substituents of C _1-6 alkyl”, may be 1 to 3 substituents, 1 to 2 substituents, 2 substituents, or 1 substituent.

[0233] In some embodiments, in conjunction with embodiments above or below, wherein when B is optionally substituted with one or more R ^t , R ^t is C _1-15 alkoxy optionally substituted with 1-3 halo. In some embodiments, in conjunction with embodiments above or below, R ^t is C _1-15 alkoxy substituted with 1-3 halo. In some embodiments, in conjunction with embodiments above or below, R ^t is OCF ₃

[0234] In some embodiments, in conjunction with embodiments above or below, wherein when X ¹ is CR ^s , R ^s is , or a stereoisomer thereof. In some embodiments, R ^s is

[0235] In some embodiments, in conjunction with embodiments above or below, n and m are each 1.

[0236] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A-l) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , L, and Z of formula (A-l) are as defined in formula (I- AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , L, and Z of formula (A-l) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , L, and Z of formula (A-l) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , L, and Z of formula (A-l) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , L, and Z described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (A-l). [0237] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (B-l) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , and Z of formula (B-l) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , and Z of formula (B-l) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , and Z of formula (B-l) are as defined in formula (B). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , and Z of formula (B-l) are as defined in formula (B’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , and Z described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (B-l).

[0238] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-1) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-1) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-1) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-1) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-1) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-1).

[0239] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-2) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , L, and R ^c of formula (I-A-2) are as defined in formula (I- AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , L, and R ^c of formula (I-A-2) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , L, and R ^c of formula (I-A-2) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , L, and R ^c of formula (I-A-2) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , L, and R ^c described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-2).

[0240] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-3) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , and B of formula (I-A-3) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and B of formula (I-A-3) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and B of formula (I-A-3) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and B of formula (I-A-3) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , and B described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-3).

[0241] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-4) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , L, and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-4).

[0242] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (A-la) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (A- la) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (A- la) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (A-la) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (A-la) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , L, and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (A-la).

[0243] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (B-la) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , n, m, and Z of formula (B-la) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , n, m, and Z of formula (B-la) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , n, m, and Z of formula (B-la) are as defined in formula (B). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , n, m, and Z of formula (B-la) are as defined in formula (B’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , n, m, and Z described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (B-1a).

[0244] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-la) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-la) are as defined in formula (I- AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-la) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-la) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t of formula (I-A-la) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , L, and R ^t described for formula (I- AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-1a).

[0245] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-4a) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4a) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4a) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4a) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , L, and R ^t of formula (I-A-4a) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , L, and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-4a).

[0246] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-5) is provided:

In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-5) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-5) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-5) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-5) are as defined in formula (A). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-5) are as defined in formula (A’). It is understood that embodiments of R ^s , R ^a , R ^b , L, B, and R ^c described for formula (I-AB), (AB), (AB’), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-5).

[0247] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-6) is provided:

In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-6) are as defined in formula (I-AB). In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-6) are as defined in formula (AB). In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-6) are as defined in formula (A). In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-6) are as defined in formula (A’). It is understood that embodiments of R ^a , R ^b , L, B, and R ^c described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-6).

[0248] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-7) is provided:

In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-7) are as defined in formula (I-AB). In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-7) are as defined in formula (AB). In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-7) are as defined in formula (A). In one aspect, R ^a , R ^b , L, B, and R ^c of formula (I-A-7) are as defined in formula (A’). It is understood that embodiments of R ^a , R ^b , L, B, and R ^c described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-7).

[0249] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-8) is provided: In one aspect, L and B of formula (I-A-B) are as defined in formula (I-AB). In one aspect, L and B of formula (I-A-B) are as defined in formula (AB). In one aspect, L and B of formula (I-A-B) are as defined in formula (A). In one aspect, L and B of formula (I-A-B) are as defined in formula (A’). It is understood that embodiments of L and B described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-8).

[0250] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-9) is provided:

In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-9) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-9) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-9) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-9) are as defined in formula (A). In one aspect, R ^s , R ^a , R ^b , L, B, and R ^c of formula (I-A-9) are as defined in formula (A’). It is understood that embodiments of R ^s , R ^a , R ^b , L, B, and R ^c described for formula (I-AB), (AB), (AB’), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-9).

[0251] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A- 10) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-10) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A- 10) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A- 10) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-10) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-10).

[0252] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-11) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-11).

[0253] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A’-11) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) or (I-A’-11) are as defined in formula (I- AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) or (I-A’-11) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) or (I-A’-11) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11) or (I-A’-11) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-11) or (I-A’-11). [0254] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-10a) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-10a) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-10a) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-10a) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-10a) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-10a).

[0255] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-11a) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-11a).

[0256] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-11a) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) or (I-A’-11a) are as defined in formula (I- AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) or (I-A’-11a) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) or (I-A’-11a) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , and R ^t of formula (I-A-11a) or (I-A’-11a) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , and R ^t described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-11a) or (I-A’-11a).

[0257] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-12) is provided:

In one aspect, R ^s , R ^a , R ^b , L, and R ^c of formula (I-A-12) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , L, and R ^c of formula (I-A-12) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , L, and R ^c of formula (I-A-12) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , L, and R ^c of formula (I-A-12) are as defined in formula (A). In one aspect, R ^s , R ^a , R ^b , L, and R ^c of formula (I-A-12) are as defined in formula (A’). It is understood that embodiments of R ^s , R ^a , R ^b , L, and R ^c described for formula (I-AB), (AB), (AB’), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-12).

[0258] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-13) is provided:

In one aspect, R ^s , R ^t , R ^a , R ^b , and R ^c of formula (I-A-13) are as defined in formula (I- AB). In one aspect, R ^s , R ^t , R ^a , R ^b , and R ^c of formula (I-A-13) are as defined in formula (AB). In one aspect, R ^s , R ^t , R ^a , R ^b , and R ^c of formula (I-A-13) are as defined in formula (AB’). In one aspect, R ^s , R ^t , R ^a , R ^b , and R ^c of formula (I-A-13) are as defined in formula (A). In one aspect, R ^s , R ^t , R ^a , R ^b , and R ^c of formula (I-A-13) are as defined in formula (A’). It is understood that embodiments of R ^s , R ^t , R ^a , R ^b , and R ^c described for formula (I-AB), (AB), (AB’), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-13).

[0259] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-14) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , Z, L, and R ¹ of formula (I-A-14) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , Z, L, and R ¹ of formula (I-A-14) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , Z, L, and R ¹ of formula (I-A-14) are as defined in formula (A). In one aspect, X ¹ , X ² , X ³ , X ⁴ , Z, L, and R ¹ of formula (I-A-14) are as defined in formula (A’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , Z, L, and R ¹ described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-14).

[0260] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-15) is provided:

In one aspect, R ^s , Z, L, and R ¹ of formula (I-A- 15) are as defined in formula (I-AB). In one aspect, R ^s , Z, L, and R ¹ of formula (I-A- 15) are as defined in formula (AB). In one aspect, R ^s , Z, L, and R ¹ of formula (I-A-15) are as defined in formula (AB’). In one aspect, R ^s , Z, L, and R ¹ of formula (I-A- 15) are as defined in formula (A). In one aspect, R ^s , Z, L, and R ¹ of formula (I-A- 15) are as defined in formula (A’). It is understood that embodiments of R ^s , Z, L, and R ¹ described for formula (I-AB), (AB), (AB’), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-15).

[0261] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-16) is provided:

In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-A-16) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-A-16) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-A-16) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-A-16) are as defined in formula (A). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-A-16) are as defined in formula (A’). It is understood that embodiments of R ^s , R ^a , R ^b , and R ^c described for formula (I-AB), (AB), (AB’), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-16).

[0262] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-17) is provided:

In one aspect, R ^s , Z, L, B, and R ¹ of formula (I-A-17) are as defined in formula (I-AB). In one aspect, R ^s , Z, L, B, and R ¹ of formula (I-A-17) are as defined in formula (AB). In one aspect, R ^s , Z, L, B, and R ¹ of formula (I-A-17) are as defined in formula (AB’). In one aspect, R ^s , Z, L, B, and R ¹ of formula (I-A-17) are as defined in formula (A). In one aspect, R ^s , Z, L, B, and R ¹ of formula (I-A-17) are as defined in formula (A’). It is understood that embodiments of R ^s , Z, L, B, and R ¹ described for formula (I-AB), (AB), (AB’), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A- 17).

[0263] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-18) is provided:

In one aspect, Z, L, B, and R ¹ of formula (I-A-18) are as defined in formula (I-AB). In one aspect, Z, L, B, and R ¹ of formula (I-A-18) are as defined in formula (AB). In one aspect, Z, L, B, and R ¹ of formula (I-A-18) are as defined in formula (A). In one aspect, Z, L, B, and R ¹ of formula (I-A- 18) are as defined in formula (A’). It is understood that embodiments of Z, L, B, and R ¹ described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-18).

[0264] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-19) is provided:

In one aspect, Z, L, B, and R ¹ of formula (I-A-19) are as defined in formula (I-AB). In one aspect, Z, L, B, and R ¹ of formula (I-A-19) are as defined in formula (AB). In one aspect, Z, L, B, and R ¹ of formula (I-A-19) are as defined in formula (A). In one aspect, Z, L, B, and R ¹ of formula (I-A- 19) are as defined in formula (A’). It is understood that embodiments of Z, L, B, and R ¹ described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-19).

[0265] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-20) is provided:

In one aspect, Z, L, B, R ^d , R ^e , and R ¹ of formula (I-A-20) are as defined in formula (I-AB). In one aspect, Z, L, B, R ^d , R ^e , and R ¹ of formula (I-A-20) are as defined in formula (AB). In one aspect, Z, L, B, R ^d , R ^e , and R ¹ of formula (I-A-20) are as defined in formula (A). In one aspect, Z, L, B, R ^d , R ^e , and R ¹ of formula (I-A-20) are as defined in formula (A’). It is understood that embodiments of Z, L, B, R ^d , R ^e , and R ¹ described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-20).

[0266] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-A-21) is provided:

In one aspect, Z, L, B, and R ¹ of formula (I-A-21) are as defined in formula (I-AB). In one aspect, Z, L, B, and R ¹ of formula (I-A-21) are as defined in formula (AB). In one aspect, Z, L, B, and R ¹ of formula (I-A-21) are as defined in formula (A). In one aspect, Z, L, B, and R ¹ of formula (I-A- 21) are as defined in formula (A’). It is understood that embodiments of Z, L, B, and R ¹ described for formula (I-AB), (AB), (A), or (A’) may, where applicable, apply in some embodiments to formula (I-A-21).

[0267] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-1) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-1) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-1) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-l) are as defined in formula (B). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-l) are as defined in formula (B’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-1).

[0268] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-2) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-2) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-2) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-2) are as defined in formula (B). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-2) are as defined in formula (B’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-2).

[0269] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-2) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and B of formula (I-B-3) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and B of formula (I-B-3) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and B of formula (I-B-3) are as defined in formula (B). In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and B of formula (I-B-3) are as defined in formula (B’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , n, m, and B described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-3).

[0270] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-4) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-4) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-4) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-4) are as defined in formula (B). In one aspect, X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t of formula formula (I-B-4) are as defined in (B’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , R ^t , R ^a , R ^b , R ^c , n, m, and R ^t described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-4).

[0271] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-5) is provided:

In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-5) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-5) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-5) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-5) are as defined in formula (B). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-5) are as defined in formula (B’). It is understood that embodiments of R ^s , R ^a , R ^b , R ^c , n, m, and B described for formula (I-AB), (AB), (AB’), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-5).

[0272] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-6) is provided:

In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-6) are as defined in formula (I-AB). In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-6) are as defined in formula (AB). In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-6) are as defined in formula (B). In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-6) are as defined in formula (B’). It is understood that embodiments of R ^a , R ^b , R ^c , n, m, and B described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-6).

[0273] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-7) is provided:

In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-7) are as defined in formula (I-AB). In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-7) are as defined in formula (AB). In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-7) are as defined in formula (B). In one aspect, R ^a , R ^b , R ^c , n, m, and B of formula (I-B-7) are as defined in formula (B’). It is understood that embodiments of R ^a , R ^b , R ^c , n, m, and B described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-7).

[0274] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-8) is provided:

In one aspect, n, m, and B of formula (I-B-8) are as defined in formula (I-AB). In one aspect, n, m, and B of formula (I-B-8) are as defined in formula (AB). In one aspect, n, m, and B of formula (I-B-8) are as defined in formula (B). In one aspect, n, m, and B of formula (I-B-8) are as defined in formula (B’). It is understood that embodiments of n, m, and B described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-8).

[0275] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-9) is provided:

In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-9) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-9) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-9) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-9) are as defined in formula (B). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and B of formula (I-B-9) are as defined in formula (B’). It is understood that embodiments of R ^s , R ^a , R ^b , R ^c , n, m, and B described for formula (I-AB), (AB), (AB’), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-9).

[0276] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-10) is provided: In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-10) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-10) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-10) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-10) are as defined in formula (B). In one aspect, R ^s , R ^a , R ^b , R ^c , n, m, and R ^t of formula (I-B-10) are as defined in formula (B’). It is understood that embodiments of R ^s , R ^a , R ^b , R ^c , n, m, and R ^t described for formula (I-AB), (AB), (AB’), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-10).

[0277] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-11) is provided:

In one aspect, R ^s , R ^a , R ^b , R ^c , and R ^t of formula (I-B-11) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , R ^c , and R ^t of formula (I-B-11) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , R ^c , and R ^t of formula (I-B-11) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , R ^c , and R ^t of formula (I-B-11) are as defined in formula (B). In one aspect, R ^s , R ^a , R ^b , R ^c , and R ^t of formula (I-B-11) are as defined in formula (B’). It is understood that embodiments of R ^s , R ^a , R ^b , R ^c , and R ^t described for formula (I-AB), (AB), (AB’), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-11).

[0278] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-12) is provided:

In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and Z of formula (I-B-12) are as defined in formula (I-AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and Z of formula (I-B-12) are as defined in formula (AB). In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and Z of formula (I-B-12) are as defined in formula (B). In one aspect, X ¹ , X ² , X ³ , X ⁴ , n, m, and Z of formula (I-B-12) are as defined in formula (B’). It is understood that embodiments of X ¹ , X ² , X ³ , X ⁴ , n, m, and Z described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-12).

[0279] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-13) is provided:

In one aspect, R ^s , n, m, and Z of formula (I-B-13) are as defined in formula (I-AB). In one aspect, R ^s , n, m, and Z of formula (I-B-13) are as defined in formula (AB). In one aspect, R ^s , n, m, and Z of formula (I-B-13) are as defined in formula (AB’). In one aspect, R ^s , n, m, and Z of formula (I- B-13) are as defined in formula (B). In one aspect, R ^s , n, m, and Z of formula (I-B-13) are as defined in formula (B’). It is understood that embodiments of R ^s , n, m, and Z described for formula (I-AB), (AB), (AB’), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-13).

[0280] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-14) is provided:

In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-B-14) are as defined in formula (I-AB). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-B-14) are as defined in formula (AB). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-B-14) are as defined in formula (AB’). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-B-14) are as defined in formula (B). In one aspect, R ^s , R ^a , R ^b , and R ^c of formula (I-B-14) are as defined in formula (B’). It is understood that embodiments of R ^s , R ^a , R ^b , and R ^c described for formula (I-AB), (AB), (AB’), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-14). [0281] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-15) is provided:

In one aspect, R ^s , n, m, B, and Z of formula (I-B-15) are as defined in formula (I-AB). In one aspect, R ^s , n, m, B, and Z of formula (I-B-15) are as defined in formula (AB). In one aspect, R ^s , n, m, B, and Z of formula (I-B-15) are as defined in formula (AB’). In one aspect, R ^s , n, m, B, and Z of formula (I-B-15) are as defined in formula (B). In one aspect, R ^s , n, m, B, and Z of formula (I-B-15) are as defined in formula (B’). It is understood that embodiments of R ^s , n, m, B, and Z described for formula (I- AB), (AB), (AB’), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-15).

[0282] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-16) is provided:

In one aspect, B, n, m, and Z of formula (I-B-16) are as defined in formula (I- AB). In one aspect, B, n, m, and Z of formula (I-B-16) are as defined in formula (AB). In one aspect, B, n, m, and Z of formula (I-B-16) are as defined in formula (B). In one aspect, B, n, m, and Z of formula (I-B- 16) are as defined in formula (B’). It is understood that embodiments of B, n, m, and Z described for formula (I- AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-16).

[0283] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-17) is provided:

In one aspect, B, n, m, and Z of formula (I-B-17) are as defined in formula (I-AB). In one aspect, B, n, m, and Z of formula (I-B-17) are as defined in formula (AB). In one aspect, B, n, m, and Z of formula (I-B-17) are as defined in formula (B). In one aspect, B, n, m, and Z of formula (I-B- 17) are as defined in formula (B’). It is understood that embodiments of B, n, m, and Z described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-17).

[0284] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-18) is provided:

In one aspect, B, n, m, R ^d , R ^e , and Z of formula (I-B-18) are as defined in formula (I- AB). In one aspect, B, n, m, R ^d , R ^e , and Z of formula (I-B-18) are as defined in formula (AB). In one aspect, B, n, m, R ^d , R ^e , and Z of formula (I-B-18) are as defined in formula (B). In one aspect, B, n, m, R ^d , R ^e , and Z of formula (I-B-18) are as defined in formula (B’). It is understood that embodiments of B, n, m, R ^d , R ^e , and Z described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-18).

[0285] In some aspects, a compound or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof of the following formula (I-B-19) is provided:

In one aspect, B, n, m, and Z of formula (I-B-19) are as defined in formula (I- AB). In one aspect, B, n, m, and Z of formula (I-B-19) are as defined in formula (AB). In one aspect, B, n, m, and Z of formula (I-B-19) are as defined in formula (B). In one aspect, B, n, m, and Z of formula (I-B- 19) are as defined in formula (B’). It is understood that embodiments of B, n, m, R ^d , R ^e , and Z described for formula (I-AB), (AB), (B), or (B’) may, where applicable, apply in some embodiments to formula (I-B-19).

[0286] Certain TEAD inhibitors described herein may exhibit reduced off-target inhibition, such as inhibition of the cardiac sodium channel (e.g., NaV _1.5 ). In some embodiments, the NaV _1.5 inhibition is measured by an assay described herein, such as an assay described in one or more examples.

[0287] In some aspects, compounds of formula (I-AB), (AB), (AB’), (A), (B), (A’), (B’), (I-A), or (I-B) or any variation or embodiment thereof, as appropriate, are selected from the compounds listed in Table 1 below, including racemic mixtures and resolved isomers:

Table 1

[0288] Provided herein is a compound selected from the group consisting of:

N-((1-(4-(trifluoromethoxy)phenyl)-1H-indazol-3-yl)methyl )acrylamide,

2-chloro-N-((1-(4-(trifluoromethoxy)phenyl)-1H-indazol-3- yl)methyl)acetamide,

N-((1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide,

N-((4-(hydroxymethyl)-1-(4-(trifluoromethoxy)phenyl)-1H-i ndazol-3-yl)methyl)acrylamide,

N-((4-(hydroxymethyl)-1-(4-(pentafluoro-λ6-sulfaneyl)phe nyl)-1H-indazol-3- yl)methyl)acrylamide,

N-((4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phenyl) -1H-indazol-3-yl)methyl)acrylamide, (R)-N-((4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phenyl )-1H-indazol-3- yl)methyl)acrylamide,

(S)-N-((4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-indazol-3- yl)methyl)acrylamide, N-((4-(1,2-dihydroxyethyl)-1-(4-(pentafluoro-λ6-sulfaneyl)p henyl)-1H-indazol-3- yl)methyl)acrylamide,

(R)-N-((4-(1,2-dihydroxyethyl)-1-(4-(pentafluoro-λ6-sulf aneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide,

(S)-N-((4-(1,2-dihydroxyethyl)-1-(4-(pentafluoro-λ6-sulf aneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide, N-((1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-pyrazolo[4,3- b]pyridin-3-yl)methyl)acrylamide, N-((1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)methyl)acrylamide, N-((4-cyano-1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-indaz ol-3-yl)methyl)acrylamide, N-[[4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phenyl)-1H -pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide,

(R)-N-[[4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide,

(S)-N-[[4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide, N-methyl-N-((1-(4-(trifluoromethoxy)phenyl)-1H-indazol-3-yl) methyl)acrylamide, and 2-chloro-N-methyl-N-((1-(4-(trifluoromethoxy)phenyl)-1H-inda zol-3-yl)methyl)acetamide, or a pharmaceutically acceptable salt thereof. Also provided herein are, where applicable, any and all stereoisomers of the compounds depicted herein, including geometric isomers (e.g., cis/trans isomers or E/Z isomers), enantiomers, diastereomers, tautomers, or mixtures thereof in any ratio, including racemic mixtures.

[0289] Provided herein is a compound selected from the group consisting of:

N-((1-(4-(trifluoromethoxy)phenyl)-1H-indazol-3-yl)methyl )acrylamide;

2-chloro-N-((1-(4-(trifluoromethoxy)phenyl)-1H-indazol-3- yl)methyl)acetamide;

N-((1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide;

N-((4-(hydroxymethyl)-1-(4-(trifluoromethoxy)phenyl)-1H-i ndazol-3-yl)methyl)acrylamide;

N-((4-(hydroxymethyl)-1-(4-(pentafluoro-λ6-sulfaneyl)phe nyl)-1H-indazol-3- yl)methyl)acrylamide;

N-((4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phenyl) -1H-indazol-3-yl)methyl)acrylamide; (R)-N-((4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phenyl )-1H-indazol-3- yl)methyl)acrylamide;

(S)-N-((4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-indazol-3- yl)methyl)acrylamide;

N-((4-(1,2-dihydroxyethyl)-1-(4-(pentafluoro-λ6-sulfaney l)phenyl)-1H-indazol-3- yl)methyl)acrylamide;

(R)-N-((4-(1,2-dihydroxyethyl)-1-(4-(pentafluoro-λ6-sulf aneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide;

(S)-N-((4-(1,2-dihydroxyethyl)-1-(4-(pentafluoro-λ6-sulf aneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide;

N-((1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-pyrazolo[4 ,3-b]pyridin-3-yl)methyl)acrylamide;

N-((1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-pyrazolo[3 ,4-b]pyridin-3-yl)methyl)acrylamide;

N-((4-cyano-1-(4-(pentafluoro-λ6-sulfaneyl)phenyl)-1H-in dazol-3-yl)methyl)acrylamide;

N-[[4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phenyl) -1H-pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide;

(R)-N-[[4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide;

(S)-N-[[4-(1,2-dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide;

N-methyl-N-((1-(4-(trifluoromethoxy)phenyl)-1H-indazol-3- yl)methyl)acrylamide;

2-chloro-N-methyl-N-((1-(4-(trifluoromethoxy)phenyl)-1H-i ndazol-3-yl)methyl)acetamide;

2-fluoro-1-[3-[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)p henyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]prop-2-en-1-one;

1-[3 -[4-[(1R)-1,2-dihydroxyethyl]-1-[4-(trifluoromethoxy)phenyl] pyrazolo[3,4-b]pyridin-3- yl]azetidin- 1 -yl]-2-fluoro-prop-2-en- 1 -one;

1-[3 -[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3 ,4-b]pyridin-3-yl]azetidin-1- yl]-2-methyl-prop-2-en-1-one; N-[[1-[4-(pentafluoro-lambda6-sulfanyl)phenyl]-4-[rac-(lS)-1 ,2-dihydroxyethyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

N-[[4-[(2-hydroxyacetyl)amino]-1-[4-(trifluoromethoxy)phe nyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide; N-(2 -hydroxyethyl)-3-[(prop-2-enoylamino)methyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridine-4-carboxami de;

(Z)-3-chloro-N-[[4-[(1R)-1,2-dihydroxyethyl]-1-[4-(triflu oromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide; N-[[1-[4-(pentafluoro-lambda6-sulfanyl)phenyl]-4-[rac-(1R)-1 ,2-dihydroxyethyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

2-fluoro-1-[3-[4-[1-(2-hydroxyethyl)pyrazol-4-yl]-1-[4-(t rifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one;

2-fluoro-1-[3-[4-(1,2,4-triazol-4-yl)-1-[4-(trifluorometh oxy)phenyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]prop-2-en-1-one;

N-methyl-3-[(prop-2-enoylamino)methyl]-1-[4-(trifluoromet hoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carboxamide;

1-[3-[4-[(1S)-1,2-dihydroxyethyl]-1-[4-(trifluoromethoxy) phenyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one;

N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyraz olo[3,4-b]pyridin-3-yl]methyl]prop- 2-enamide;

N-[[4-[(3S)-3-hydroxy-1-piperidyl]-1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(3-hydroxycyclobutoxy)-1-[4-(trifluoromethoxy)pheny l]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[1-(2-hydroxyethyl)pyrazol-4-yl]-1-[4-(trifluoromet hoxy)phenyl]pyrazolo[3,4-b]pyridin- 3-yl]methyl]prop-2-enamide;

N-[[4-(2-hydroxyethylamino)-1-[4-(trifluoromethoxy)phenyl ]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(E)-3-chloro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(3-hydroxycyclobutyl)-1-[4-(trifluoromethoxy)phenyl ]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

2-fluoro-1-[3-[4-[3 -fluoro-3-(hydroxymethyl)azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidi n-1-yl]prop-2-en-1-one; (E)-1-[3-[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]py razolo[3,4-b]pyridin-3- yl]azetidin-1-yl]-4-methoxy-but-2-en-1-one; 1-[3-[4-(2,6-diazaspiro[3.3]heptan-2-yl)-1-[4-(trifluorometh oxy)phenyl]pyrazolo[3,4-b]pyridin-

3 -yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one;

N-[3-[1-(2-fluoroprop-2-enoyl)azetidin-3-yl]-1-[4-(triflu oromethoxy)phenyl]pyrazolo[3,4- b]pyridin-4-yl]-2-hydroxy-acetamide;

N-[[4-[3-(hydroxymethyl)azetidin-1-yl]-1-[4-(trifluoromet hoxy)phenyl]pyrazolo[3,4-b]pyridin- 3-yl]methyl]prop-2-enamide;

N-[[4-(1H-1,2,4-triazol-3-yl)-1-[4-(trifluoromethoxy)phen yl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide; 1-[3-[4-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-1-[4-(trifl uoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one;

N-[[4-[(3S)-3-hydroxypyrrolidin-1-yl]-1-[4-(trifluorometh oxy)phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[(3R)-3-hydroxypyrrolidin-1-yl]-1-[4-(trifluorometh oxy)phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide; 1-[3-[4-ethynyl-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b ]pyridin-3-yl]azetidin-1-yl]prop-2- en-1-one;

2-chloro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phe nyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(E)-4-hydroxy-1-[3-[4-(1H-pyrazol-4-yl)-1-[4-(trifluorome thoxy)phenyl]pyrazolo[3,4-b]pyridin- 3 -yl]azetidin-1-yl]but-2-en-1-one;

N-[[4-(1H-triazol-4-yl)-1-[4-(trifluoromethoxy)phenyl]pyr azolo[3,4-b]pyridin-3-yl]methyl]prop-

2-enamide;

N-[[4-(3-cyanoazetidin-1-yl)-1-[4-(trifluoromethoxy)pheny l]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(Z)-3-chloro-N-[[4-[(1S)-1,2-dihydroxyethyl]-1-[4-(triflu oromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

N-[[4-[(3-hydroxyazetidin-1-yl)methyl]-1-[4-(trifluoromet hoxy)phenyl]pyrazolo[3,4-b]pyridin-

3-yl]methyl]prop-2-enamide; N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo [3,4-b]pyridin-3-yl]methyl]-N- methyl-prop-2-enamide;

N-[[4-(3-hydroxycyclobutyl)-1-[4-(trifluoromethoxy)phenyl ]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

3-fluoro-1-[3-[1-(2-fluoroprop-2-enoyl)azetidin-3-yl]-1-[ 4- (trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-4-yl]azetidi ne-3-carboxamide; 1-[3-[4-[3-[(1R)-1,2-dihydroxyethyl]azetidin-1-yl]-1-[4-(tri fluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one;

1-[3-[4-[(1S)-1,2-dihydroxyethyl]-1-[4-(pentafluoro-lambd a6-sulfanyl)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one;

1-[3-[4-[(1R)-1,2-dihydroxyethyl]-1-[4-(pentafluoro-lambd a6-sulfanyl)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one;

(E)-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]p yrazolo[3,4-b]pyridin-3- yl]methyl]but-2-enamide;

N-[[4-[(1R)-1-hydroxyethyl]-1-[4-(trifluoromethoxy)phenyl ]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[(l S)-1-hydroxy ethyl]-1-[4-(tri fluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

2-fluoro-1-[3-[4-imidazol-1-yl-1-[4-(trifluoromethoxy)phe nyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]prop-2-en-1-one;

N-[[4-[(3R)-3-hydroxy-1-piperidyl]-1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(E,4R)-4-hydroxy-1-[3-[4-(hydroxymethyl)-1-[4-(trifluorom ethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]pent-2-en-1-one;

N-[[4-(3-hydroxycyclobutoxy)-1-[4-(trifluoromethoxy)pheny l]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

2-fluoro-N-[[4-(hydroxymethyl)-1-[4-(trifluorornethoxy)ph enyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(E)-4,4-difluoro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromet hoxy)phenyl]pyrazolo[3,4-b]pyridin-

3-yl]methyl]but-2-enamide; (E)-4-hydroxy-1-[3-[4-(3-hydroxyazetidin-1-yl)-1-[4-(trifluo romethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-en-1-one;

1-[3-[4-[(1R)-1,2-dihydroxyethyl]-1-[4-(trifluoromethoxy) phenyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]but-2-yn-1-one; cyclobuten-1-y1-[3-[4-[(lS)-1,2-dihydroxyethyl]-1-[4-(triflu oromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]methanone;

N-[[4-[rac-(lS)-1,2-dihydroxyethyl]-1-[3-(trifluoromethox y)phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(3-hydroxy-3-methyl-azetidin-1-yl)-1-[4-(trifluorom ethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

2-fluoro-1-[3-[4-[3-hydroxy-3-(hydroxymethyl)azetidin-1-y l]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidi n-1-yl]prop-2-en-1-one;

N-[[4-(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)-1-[4-(triflu oromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

N-[[4-morpholino-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3 ,4-b]pyridin-3-yl]methyl]prop-2- enamide;

2-fluoro-1-[3-[4-(3-hydroxyazetidin-1-yl)-1-[4-(trifluoro methoxy)phenyl]pyrazolo[4,3- c]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one;

3-[1-[(E)-4-hydroxybut-2-enoyl]azetidin-3-yl]-1-[4-(trifl uoromethoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carbonitrile;

3-[1-(2-fluoroprop-2-enoyl)azetidin-3-yl]-1-[4-(trifluoro methoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carbonitrile;

2-fluoro-1-[3-[4-(3-hydroxyazetidin-1-yl)-1-[4-(trifluoro methoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one;

(3S)-1-[3-[1-(2-fluoroprop-2-enoyl)azetidin-3-yl]-1-[4-(t rifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-4-yl]-3-hydroxy-pyrrolidin-2-one;

N-[[4-(1H-pyrazol-3-yl)-1-[4-(trifluoromethoxy)phenyl]pyr azolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(3-fluoroazetidin-1-yl)-1-[4-(trifluoromethoxy)phen yl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide; N-[[4-[(3-hydroxycyclobutyl)amino]-1-[4-(trifluoromethoxy)ph enyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyraz olo[3,4-b]pyridin-3-yl]methyl]prop- 2-ynamide;

N-[[4-(hydroxymethyl)-1-[4-(pentafluoro-lambda6-sulfanyl) phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[rac-(1R)-1,2-dihydroxyethyl]-1-[4-(trifluoromethyl )phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide; cyclobuten-1-y1-[3-[4-(hydroxymethyl)-1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin- 1 -yl]methanone;

N-[[4-[(3-hydroxycyclobutyl)-methyl-amino]-1-[4-(trifluor omethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

N-[[4-(4-hydroxy-1-piperidyl)-1-[4-(trifluoromethoxy)phen yl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(3-aminoazetidin-1-yl)-1-[4-(trifluoromethoxy)pheny l]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[(1R)-1,2-dihydroxyethyl]-1-[4-(trifluoromethoxy)ph enyl]pyrazolo[3,4-b]pyridin-3- yl ] methyl] -N -methyl -prop-2-enami de;

(E)-4-hydroxy-1-[3-[4-(hydroxymethyl)-1-[4-(trifluorometh oxy)phenyl]pyrazolo[3,4-b]pyridin- 3 -yl]azetidin-1-yl]but-2-en-1-one;

(E)-1-[3-[4-[(1R)-1,2-dihydroxyethyl]-1-[4-(trifluorometh oxy)phenyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]-4-hydroxy-but-2-en-1-one;

(E)-4-hydroxy-1-[3-[4-methyl-1-[4-(trifluoromethoxy)pheny l]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]but-2-en-1-one;

(E,4S)-4-hydroxy-1-[3-[4-(hydroxymethyl)-1-[4-(trifluorom ethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]pent-2-en-1-one;

N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyraz olo[3,4-b]pyridin-3-yl]methyl]but- 2-ynamide;

(Z)-3-chloro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide; N-[[4-[rac-(lS)-1,2-dihydroxyethyl]-1-[4-(trifluoromethyl)ph enyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[2 -hydroxy ethyl(methyl)amino]-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3 ,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(E)-3-chloro-1-[3-[4-(hy droxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]py ridin-3- yl]azetidin-1-yl]prop-2-en-1-one;

(E)-4-hydroxy-1-[3-[4-(3-hydroxyazetidin-1-yl)-1-[4-(trif luoromethoxy)phenyl]pyrazolo[4,3- c]pyridin-3-yl]azetidin-1-yl]but-2-en-1-one;

3-[(prop-2-enoylamino)methyl]-1-[4-(trifluoromethoxy)phen yl]pyrazolo[3,4-b]pyridine-4- carboxamide;

N-[[4-[(dimethylamino)methyl]-1-[4-(trifluoromethoxy)phen yl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(3 -hydroxyazetidin-1-yl)-1-[4-(trifluorom ethoxy )phenyl]pyrazolo[3,4-b]pyridin-3 - yl]methyl]prop-2-enamide;

N-[[4-[3-(dimethylamino)azetidin-1-yl]-1-[4-(trifluoromet hoxy)phenyl]pyrazolo[3,4-b]pyridin- 3-yl]methyl]prop-2-enamide;

(E)-1-[3-[4-[(lS)-1,2-dihydroxyethyl]-1-[4-(trifluorometh oxy)phenyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin- 1 -yl]-4-hydroxy-but-2-en- 1 -one;

2-chloro-1-[3-[4-[(l S)-1,2-dihydroxy ethyl]-1-[4-(tri fluoromethoxy )phenyl]pyrazolo[3, 4- b]pyridin-3 -yl]azetidin- 1 -yl]prop-2-en- 1 -one;

2-chloro-1 -[3-[4-[(1R)-1,2-dihydroxy ethyl]-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3 -yl]azetidin- 1 -yl]prop-2-en- 1 -one;

2, 3, 3-trideuterio-N-[[4-(hydroxymethyl)-1-[4-(tri fluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin- 3-yl]methyl]prop-2-enamide;

1 -[3 -[4-(hydroxymethyl)-1 -[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]aze tidin-1- yl]prop-2-en-1-one;

1 -[3 -[4-[(1S)- 1,2-dihydroxyethyl]- 1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin-1-yl]prop-2-en- 1 -one;

1 -[3 -[4-[(1R)- 1 ,2-dihydroxy ethyl]- 1 -[4-(trifluoromethoxy)phenyl]pyrazolo[3 ,4-b]pyridin-3 - yl]azetidin-1-yl]prop-2-en-1-one; cyclobuten-1-y1-[3-[4-[(1R)-1,2-dihydroxyethyl]-1-[4-(triflu oromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]methanone;

N-[[4-(3-acetamidoazetidin-1-yl)-1-[4-(trifluoromethoxy)p henyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[(3-hydroxycyclobutyl)-methyl-amino]-1-[4-(trifluor omethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

N-[[4-(3 -m ethoxy azetidin- 1 -yl)- 1 -[4-(trifluoromethoxy)phenyl]pyrazolo[3 ,4-b]pyridin-3 - yl]methyl]prop-2-enamide;

N-[[4-(1H-imidazol-4-yl)-1-[4-(trifluoromethoxy)phenyl]py razolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(E)-1-[3-[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl ]pyrazolo[3,4-b]pyridin-3- yl]azetidin- 1 -yl]but-2-en- 1 -one;

(E)-4-fluoro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]but-2-enamide;

N-[[4-[3-(methylarnino)azetidin-1-yl]-1-[4-(trifluorornet hoxy)phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[3 -[( 1R)- 1 -hydroxy ethyl] azetidin- 1 -yl]- 1 -[4-(trifluoromethoxy)phenyl]pyrazolo[3 ,4- b]pyridin-3-yl]methyl]prop-2-enamide;

N-[[4-[3-hydroxy-3-(hydroxymethyl)azetidin-1-yl]-1-[4-(tr ifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

(3R)-1-[3-[1-(2-fluoroprop-2-enoyl)azetidin-3-yl]-1-[4-(t rifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-4-yl]-3-hydroxy-pyrrolidin-2-one;

N-[[4-(2 -hydroxy ethoxy)-1-[4-(tri fluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3 - yl]methyl]prop-2-enamide;

(E)-1-[3-[4-chloro-1-[4-(trifluoromethoxy)phenyl]pyrazolo [3,4-b]pyridin-3-yl]azetidin-1-yl]-4- hydroxy -but-2-en- 1 -one;

4-hydroxy-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)ph enyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]but-2-ynamide;

1 -[3 -[4-[( 1 S)- 1 ,2-dihydroxy ethyl]- 1 -[4-(trifluorom ethoxy )phenyl]pyrazolo[3 ,4-b]pyridin-3 - yl]azetidin- 1 -yl]but-2-yn- 1 -one; 2-fluoro-1-[3-[4-(1H-imidazol-4-yl)-1-[4-(trifluoromethoxy)p henyl]pyrazolo[3,4-b]pyridin-3- yl]azetidin- 1 -yl]prop-2-en- 1 -one;

N-[[4-[rac-(1R)-1,2-dihydroxyethyl]-1-[3-(trifluoromethox y)phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(E)-4,4,4-trifluoro-N-[[4-(hydroxymethyl)-1-[4-(trifluoro methoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-enamide;

1 -[3 -[4-(azetidin-3 -yl)- 1 -[4-(trifluorom ethoxy )phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1- yl]-2-fluoro-prop-2-en-1-one;

N-[[4-(1H-pyrazol-4-yl)-1-[4-(trifluoromethoxy)phenyl]pyr azolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-(1 -hydroxy- 1-methyl-ethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b ]pyridin-3- yl]methyl]prop-2-enamide;

N-[[4-[3 -(1 -hydroxy-1-methyl-ethyl)azetidin-1-yl]-1-[4-(trifluoromethox y)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

(E)-4-fluoro-1-[3-[4-(3-hydroxyazetidin-1-yl)-1-[4-(trifl uoromethoxy)phenyl]pyrazolo[4,3- c]pyridin-3-yl]azetidin-1-yl]but-2-en-1-one;

N-[[4-[3 -[(1S)-1-hydroxyethyl]azetidin-1-yl]-1-[4-(trifluoromethoxy) phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide;

N-[[4-[(lS)-1,2-dihydroxyethyl]-1-[4-(trifluoromethoxy)ph enyl]pyrazolo[3,4-b]pyridin-3- yl] methyl] -N -methyl -prop-2-enamide;

N-[[1-[4-(difluoromethoxy)phenyl]-4-(hydroxymethyl)pyrazo lo[3,4-b]pyridin-3-yl]methyl]prop- 2-enamide; 1-[3-[4-[3-[(lS)-1,2-dihydroxyethyl]azetidin-1-yl]-1-[4-(tri fluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one; 1-[3-[4-[3,3-bis(hydroxymethyl)azetidin-1-yl]-1-[4-(trifluor omethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro-prop-2-en-1-one;

N-[[4-[(3-hydroxycyclobutyl)amino]-1-[4-(trifluoromethoxy )phenyl]pyrazolo[3,4-b]pyridin-3- yl]methyl]prop-2-enamide;

(S)-N-((4-(2-Oxo-1,3-dioxolan-4-yl)-1-(4-(trifluoromethox y)phenyl)-1H-pyrazolo[3,4-b]pyridin-

3-yl)methyl)acrylamide; (S)-2-(3-(Acrylamidomethyl)-1-(4-(trifluoromethoxy)phenyl)-1 H-pyrazolo[3,4-b]pyridin-4-yl)- 2-hydroxyethyl 2-aminoacetate formate;

(S)-2-(3-(Acrylamidomethyl)-1-(4-(trifluoromethoxy)phenyl )-1H-pyrazolo[3,4-b]pyridin-4-yl)- 2-hydroxyethyl acetate;

(S)-2-(3-(Acrylamidomethyl)-1-(4-(trifluoromethoxy)phenyl )-1H-pyrazolo[3,4-b]pyridin-4-yl)- 2-hydroxyethyl dihydrogen phosphate;

N-((4-(Hydroxymethyl)-1-(4-(trifluoromethoxy)phenyl)-1H-p yrazolo[3,4-b]pyridin-3- yl)methyl)cyclobut- 1 -enecarboxamide;

N-((4-(Hydroxymethyl)-1-(4-(trifluoromethoxy)phenyl)-1H-p yrazolo[3,4-b]pyridin-3- yl)methyl)-2,5-dihydrofuran-3-carboxamide;

Cyclopent- 1 -en- 1 -yl(3 -(4-(hydroxym ethyl)- 1 -(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3 -yl)azetidin-1-yl)methanone;

(E)- 1 -(3 -(4-(Hydroxymethyl)- 1 -(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridin-3- yl)azetidin- 1 -yl)-2-methylbut-2-en- 1 -one;

(2,5-Dihydrofuran-3-yl)(3-(4-(hydroxymethyl)-1-(4-(triflu oromethoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3 -yl)azetidin-1-yl)m ethanone;

Bicyclo[1.1.0]butan-1-yl(3-(4-(hydroxymethyl)-1-(4-(trifl uoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1-yl)methanone;

(S)-N-((4-(1,2-Dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide-2,3,3-d3;

(S)-N-((4-(1,2-Dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-pyrazolo[3,4-b]pyridin-3- yl)methyl)-2-fluoroacrylamide;

(S)-N-((4-(1,2-Dihydroxyethyl)-1-(4-(trifluoromethoxy)phe nyl)-1H-pyrazolo[3,4-b]pyridin-3- yl)methyl)cyclobut-1-enecarboxamide;

(R)-Cyclobut-1-en-1 -yl (3 -(4-( 1 ,2-dihydroxy ethyl)- 1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1-yl)methanone;

2 -Fluoro- 1 -(3 -(4-( 1 -methyl-1H-pyrazol-4-yl)- 1 -(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3 -yl)azetidin- 1 -yl)prop-2-en- 1 -one;

(S)-1-(3-(1-(Prop-1-en-2-ylsulfonyl)azetidin-3-yl)-1-(4-( trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2-diol; (R)- 1 -(3 -(1 -(prop- 1 -en-2-ylsulfonyl)azetidin-3 -yl)- 1 -(4-(trifluoromethoxy)phenyl)- 1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2-diol;

(S,E)- 1 -(3 -( 1 -(Prop- 1 -en- 1 -ylsulfonyl)azetidin-3 -yl)- 1 -(4-(trifluoromethoxy)phenyl)- 1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2-diol;

(R,E)- 1 -(3 -(1 -(prop- 1 -en- 1 -ylsulfonyl)azetidin-3 -yl)- 1 -(4-(trifluoromethoxy)phenyl)- 1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2-diol;

Cyclobut-1-en-1-yl(3-(1-(4-(trifluoromethoxy)phenyl)-1H-p yrazolo[3,4-b]pyrazin-3-yl)azetidin- 1-yl)methanone;

N-((4-(1 -Methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-p yrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide;

N-((4-(1-(2-amino-2-oxoethyl)-1H-pyrazol-4-yl)-1-(4-(trif luoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3 -yl)methyl)acrylamide;

N-((4-(1-(2-(dimethylamino)-2-oxoethyl)-1H-pyrazol-4-yl)- 1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)methyl)acrylamide;

N-((4-(1-(2 -methoxyethyl)-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)pheny l)-1H-pyrazolo[3,4- b]pyridin-3 -yl)methyl)acrylamide;

N-((4-(1-(2-(methylsulfonyl)ethyl)-1H-pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)methyl)acrylamide;

N-((4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-(4-(trifluor omethoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)methyl)acrylamide;

N-((4-(1-isopropyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethox y)phenyl)-1H-pyrazolo[3,4-b]pyridin- 3-yl)methyl)acrylamide;

N-((4-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1-(4-(trifluorome thoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3 -yl)methyl)acrylamide;

N-((4-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)-1-(4-( trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)methyl)acrylamide;

N-((4-(1-cyclopropyl-1H-pyrazol-4-yl)-1-(4-(trifluorometh oxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)methyl)acrylamide;

1-(3-(4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-(4-(triflu oromethoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)azetidin-1-yl)-2-fluoroprop-2-en-1-one; 2-fluoro-1-(3-(4-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1-(4-(tri fluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1-yl)prop-2-en-1-one;

2-fluoro-1-(3-(4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1-( 4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1-yl)prop-2-en-1-one;

1-(3-(4-(1-cyclopropyl-1H-pyrazol-4-yl)-1-(4-(trifluorome thoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)azetidin-1-yl)-2-fluoroprop-2-en-l-one;

2-fluoro-1-(3-(4-(1-isopropyl-1H-pyrazol-4-yl)-1-(4-(trif luoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1-yl)prop-2-en-1-one;

2-fluoro-1-(3-(4-(1-(2-(methylsulfonyl)ethyl)-IH-pyrazol- 4-yl)-1-(4-(trifluoromethoxs)phenyl)- 1H-pyrazolo[3,4-b]pyridin-3-yl)azetidin-1-yl)prop-2-en-l-one ;

2-(4-(3-(1-(2-fluoroacryloyl)azetidin-3-yl)-1-(4-(trifluo romethoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-4-yl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide;

2-(4-(3-(1-(2-fluoroacryloyl)azetidin-3-yl)-1-(4-(trifluo romethoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-4-yl)-1H-pyrazol-1-yl)acetamide;

1-(3-(4-(1H-pyrazol-4-yl)-l-(4-(trifluoromethoxy)phenyl)- 1H-pyrazolo[3,4-b]pyridin-3- yl)azetidin-1-yl)-2-fluoroprop-2-en-1-one;

1-(3-(1-(2-chloro-4-(trifluoromethoxy)phenyl)-4-(hydroxym ethyl)-1H-pyrazolo[3,4-b]pyridin-3- yl)azetidin-1-yl)-2-fluoroprop-2-en-1-one;

2-fluoro1l-(3-(4-(hydroxymethyl)-1-(2-methyl-4-(trifluoro methoxy)phenyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)azetidin-1-yl)prop-2-en-1-one;

2-fluoro-1-(3-(1-(2-fluoro-4-(trifluoromethoxy)phenyl)-4- (hydroxymethyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)azetidin-1-yl)prop-2-en-1-one;

N-((4-cyano-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-3-y l)methyl)acrylamide;

N-((1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[4,3-b]pyri din-3-yl)methyl)acrylamide; and

N-((1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyri din-3-yl)methyl)acrylamide, or a pharmaceutically acceptable salt thereof. Also provided herein are, where applicable, any and all stereoisomers of the compounds depicted herein, including geometric isomers (e.g., cis/trans isomers or E/Z isomers), enantiomers, diastereomers, tautomers, or mixtures thereof in any ratio, including racemic mixtures. [0290] In one aspect, provided herein is a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, of any one of the compounds as listed in Table 1.

[0291] In one aspect, provided herein is a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, selected from the group consisting of:

[0292] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N, X ⁴ is CH, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0293] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is N, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0294] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is N, R ¹ is H, R ^s is CN, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0295] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is N, R ¹ is H, R ^s is ethyl substituted with two -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0296] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0297] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H, R ^t is methoxy substituted with three fluoro, and R ^x is ethanyl substituted by one chloro.

[0298] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro. [0299] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is methyl substituted by one -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0300] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is methyl substituted by one -OH, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0301] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is ethyl substituted by two -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0302] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is ethyl substituted by two -OH, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0303] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ^t is methoxy substituted with three fluoro, R ^x is ethenyl, and R ¹ is methyl.

[0304] In some embodiments, provided herein is a compound of formula (A) or (A’), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ^t is methoxy substituted with three fluoro, R ^x is ethanyl substituted with one chloro, and R ¹ is methyl.

[0305] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N, X ⁴ is CH, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0306] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is N, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro. [0307] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is N, R ¹ is H,R ^s is CN, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0308] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is N, R ¹ is H,R ^s is ethyl substituted with two -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0309] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H,R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0310] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H,R ^t is methoxy substituted with three fluoro, and R ^x is ethanyl substituted by one chloro.

[0311] In some embodiments, R ^x is methyl substituted by one chloro.

[0312] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H,R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0313] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H,R ^s is methyl substituted by one -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0314] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is methyl substituted by one -OH, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0315] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is ethyl substituted by two -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl. [0316] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is ethyl substituted by two -OH, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0317] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ^t is methoxy substituted with three fluoro, R ^x is ethenyl, and R ¹ is methyl.

[0318] In some embodiments, provided herein is a compound of formula (AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ^t is methoxy substituted with three fluoro, R ^x is ethanyl substituted with one chloro, and R ¹ is methyl.

[0319] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is N, X ⁴ is CH, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0320] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is N, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0321] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is N, R ¹ is H,R ^s is CN, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0322] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is N, R ¹ is H, R ^s is ethyl substituted with two -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0323] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0324] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H, R ^t is methoxy substituted with three fluoro, and R ^x is methyl substituted by one chloro. [0325] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CH, X ⁴ is CH, R ¹ is H, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0326] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is methyl substituted by one -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.

[0327] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is methyl substituted by one -OH, R ^t is S(R ^y ) ₅ , R ^x is ethenyl, and R ^y is fluoro.

[0328] In some embodiments, provided herein is a compound of formula (I-AB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ¹ is CR ^s , X ⁴ is CH, R ¹ is H, R ^s is ethyl substituted by two -OH, R ^t is methoxy substituted with three fluoro, and R ^x is ethenyl.