CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 62/883,446, filed on August 6, 2019, which is herein incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

[0002] Human ALOX-15 (15-lipoxygenase) protein is highly expressed in circulating blood eosinophils, airway epithelial cells and esophageal squamous epithelial cells. As such, ALOX- 15 inhibitors are a druggable target for treating eosinophilic airway diseases, such as asthma, chronic rhinosinusitis, nasal polyposis, and allergic rhinitis and eosinophilic diseases of the gastro-intestinal tract, such as eosinophilic esophagitis and eosinophilic gastroenteritis.

SUMMARY OF THE INVENTION

[0003] Described herein are prodrugs of ALOX-15 inhibitors. Also disclosed herein are methods for synthesizing such prodrugs and methods for using such prodrugs in the treatment of diseases wherein ALOX-15 inhibition provides therapeutic benefit to the patient having the disease. Further described are pharmaceutical formulations that include a prodrug of an ALOX- 15 inhibitor.

[0004] In one aspect is a compound having the structure of Formula (I):

Formula (I); wherein:

Ring A is selected from C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and C2-9heteroaryl; Ring B is selected from C2-9heterocycloalkyl and C2-9heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci-6alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - ryl, -OR ¹¹ , - )R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U ) ₂ , and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; eac wherein Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; n is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0005] In one aspect is a compound having the structure of Formula (II):

Formula (II); wherein:

X is a bond, Ci- ₆ alkyl, C2-6alkenyl, or C2-6alkynyl;

Ring A is selected from C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and C2-9heteroaryl; Ring B is selected from C2-9heterocycloalkyl and C2-9heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci-6alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3- 6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ )2, - C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -OC(0)R ⁸ , wherein Ci-6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - ryl, -OR ¹¹ , - )R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U ) ₂ , and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci. ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; eac N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -OC(0)R ⁸ , wherein Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁷ is -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, or Ci- 9heteroaryl, wherein C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) ₂ ; n is 0, 1, 2, 3, or 4; and p is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0006] In one aspect is a compound having the structure of Formula (III):

Formula (III); wherein:

Ring A is selected from C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and C2-9heteroaryl; Ring B is selected from C2-9heterocycloalkyl and C2-9heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci-6alkyl or -Ci-6alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3- 6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ )2, - C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -OC(0)R ⁸ , wherein Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - R ¹¹ , - Ci_ 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl;

R ¹⁶ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ ;

R ¹⁷ is C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, or Ci- ₉ heteroaryl, wherein C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0007] In one aspect is a compound having the structure of Formula (IV):

Formula (IV); wherein:

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and C _2-9 heteroaryl;

Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci. ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ¹¹ , - SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci_ 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl;

R ¹⁶ and R ¹⁷ are independently selected from H, halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , - N(R ⁶ ) ₂ , -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0008] In one aspect is a compound having the structure of Formula (V):

Formula (V); wherein:

X is Ci- ₆ alkyl;

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and C _2-9 heteroaryl;

Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ¹¹ , - SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci_ 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci. ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl;

R ¹⁶ and R ¹⁷ are independently selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- 9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ and R ¹⁹ are independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ²⁰ is C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, or Ci- ₉ heteroaryl, wherein C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0009] In one aspect is a compound having the structure of Formula (VI):

Formula (VI); wherein:

X is Ci- ₆ alkyl;

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and C _2-9 heteroaryl;

Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci-6alkyl, Ci-6haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and Ci- ₉ heteroaryl, wherein Ci-6alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3- R ¹¹ , - Ci_

₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^u ) ₂ , and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl;

R ¹⁶ and R ¹⁷ are independently selected from C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl, wherein C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci- 9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ and R ¹⁹ are independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ²⁰ is C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, or Ci-9heteroaryl, wherein C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0010] In one aspect is a compound having the structure of Formula (VII):

Formula (VII); wherein:

X is -C(0)N(R ¹⁹ )- or -N(R ¹⁹ )C(0)-;

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and C _2-9 heteroaryl;

Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - R ¹¹ , - Ci_

₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci. ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^u ) ₂ , and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; eac N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is selected from H and Ci^alkyl;

R ¹⁹ is selected from H and Ci^alkyl; n is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0011] In one aspect is a compound having the structure of Formula (VIII):

Formula (VIII); wherein:

Ring A is selected from C3- ₆ cycloalkyl, C2- ₉ heterocycloalkyl, C ₆ -ioaryl, and C2- ₉ heteroaryl; Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ² is selected from H, Ci. ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ¹¹ , - ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci-

₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^u ) ₂ , and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-cheteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2.6 alkenyl, C _2.6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; eac N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ¹⁸ is independently selected from H and Ci^alkyl; n is 0, 1, 2, 3, or 4; p is 0, 1, 2, or 3; and q is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0012] In one aspect is a compound having the structure of Formula (IX):

Formula (IX); wherein:

X is Ci-ioalkyl; Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and C _2-9 heteroaryl; Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - R ¹¹ , - Ci- 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci. ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; eac wherein Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; n is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0013] In one aspect is a compound having the structure of Formula (X):

Formula (X); wherein: each R ¹ is independently selected from -P(0)(OH) ₂ , -C(0)N(R ⁵ )C _2-6 alkyl-0C(0)R ³ ,

Ring A is selected from C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and C2-9heteroaryl; Ring B is selected from C2-9heterocycloalkyl and C2-9heteroaryl;

R ³ is selected from Ci- ₆ alkyl or -Ci-6alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C ₃ -

₆ cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ )2, -

C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl, wherein Ci- ₆ alkyl, C ₂ . 6alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ . 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl, wherein Ci- ₆ alkyl, C ₂ ^alkenyl, C ₂ .

₆ alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3- -ioaryl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ¹¹ , - ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C ₂ ^alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^u ) ₂ , and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁶ is independently selected from halogen, -CN, Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁷ is selected from H, halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ . 9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , -N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , - C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2.6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; n is 0, 1, 2, 3, or 4; and p is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0014] In another aspect described herein is a pharmaceutical composition comprising a compound of Formula (I), (la), (lb), (II), (Da), (lib), (III), (Ilia), (mb), (IV), (IVa), (IVb), (V), (Va), (Vb), (VI), (Via), (VIb), (VII), (Vila), (Vllb), (VIII), (Villa), (Vlllb), (IX), (IXa), (IXb), (X), (Xa), or (Xb), or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

[0015] Also described herein is a method of treating an eosinophilic airway disease in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), (la), (lb), (II), (Ha), (lib), (III), (Ilia), (Mb), (IV), (IVa), (IVb), (V), (Va), (Vb), (VI), (Via), (VIb), (VII), (Vila), (Vllb), (VIII), (Villa), (Vlllb), (IX), (IXa), (IXb), (X), (Xa), or (Xb), or a pharmaceutically acceptable salt or solvate thereof. In some embodiments is a method of treating an eosinophilic airway disease in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), (la), (lb), (II), (Da), (lib), (III), (Ilia), (Mb), (IV), (IVa), (IVb), (V), (Va), (Vb), (VI), (Via), (VIb), (VII), (Vila), (Vllb), (VIII), (Villa), (Vlllb), (IX), (IXa), (IXb), (X), (Xa), or (Xb), or a pharmaceutically acceptable salt or solvate thereof, wherein the eosinophilic airway disease is selected from asthma, chronic rhinosinusitis, nasal polyposis, and allergic rhinitis.

[0016] Also described herein is a method of treating an eosinophilic disease of the gastro intestinal tract in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), (la), (lb), (II), (Ha), (lib), (III), (Ilia), (Mb), (IV), (IVa), (IVb), (V), (Va), (Vb), (VI), (Via), (VIb), (VII), (Vila), (Vllb), (VIII), (Villa), (Vlllb), (IX), (IXa), (IXb), (X), (Xa), or (Xb), or a pharmaceutically acceptable salt or solvate thereof. In some embodiments is a method of treating an eosinophilic disease of the gastro-intestinal tract in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), (la), (lb), (II), (Ha), (lib), (III), (Ilia), (mb), (IV), (IVa), (IVb), (V), (Va), (Vb), (VI), (Via), (VIb), (VII), (Vila), (Vllb), (VIII), (Villa), (Vlllb), (IX), (IXa), (IXb), (X), (Xa), or (Xb), or a pharmaceutically acceptable salt or solvate thereof, wherein the eosinophilic disease of the gastro-intestinal tract is selected from eosinophilic esophagitis and eosinophilic gastritis.

DETAILED DESCRIPTION OF THE INVENTION [0017] ALOX15 is one of five (ALOX5/12/12B/15/15B) human lipoxygenases and is involved in the metabolism of arachidonic acid and other polyunsaturated fatty acid substrates. 15-HETE is its major arachidonic acid-derived metabolite, which is then further metabolized to eoxins, 5- oxo-15-hydroxy-ETE and other metabolites. ALOX15 metabolites are largely pro-inflammatory and have been shown to induce airway epithelial injury and promote goblet cell hyperplasia/mucus hypersecretion (15-HETE), increase vascular permeability (eoxin C4) and are potent eosinophil chemoattractants (5-oxo-15-hydroxy-ETE). ALOX15 is highly expressed in circulating blood eosinophils, airway epithelial cells and esophageal squamous epithelial cells and is induced in vitro by IL-13, a central mediator of the Th2 response. Accordingly, therapies as described herein designed to inhibit the production of ALOX15 protein delivered locally to the nasal epithelium, via inhalation to the airway, orally or systemically, can be efficacious in treating eosinophilic diseases of the upper and lower airway, including nasal polyposis, chronic rhinosinusitis, allergic rhinitis and asthma; and eosinophilic diseases of the gastro-intestinal tract, including eosinophilic esophagitis and eosinophilic gastroenteritis.

Definitions

[0018] As used herein and in the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or to a plurality of cells) and equivalents thereof. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulae, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. The term "about" when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range varies between 1% and 15% of the stated number or numerical range. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") is not intended to exclude that which in other certain embodiments, for example, an embodiment of any composition of matter, composition, method, or process, or the like, described herein, may "consist of or "consist essentially of" the described features.

[0019] As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated below.

[0020] As used herein, Ci-C _x includes C ₁ -C ₂ , C ₁ -C _{3 . . .} Ci-C _x. Ci-C _x refers to the number of carbon atoms that make up the moiety to which it designates (excluding optional substituents). [0021] "Amino" refers to the -NH ₂ radical.

[0022] "Cyano" refers to the -CN radical.

[0023] "Nitro" refers to the -NO ₂ radical.

[0024] "Oxa" refers to the -O- radical.

[0025] "Oxo" refers to the =0 radical.

[0026] "Thioxo" refers to the =S radical.

[0027] "Imino" refers to the =N-H radical.

[0028] "Oximo" refers to the =N-OH radical.

[0029] "Alkyl" or "alkylene" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to fifteen carbon atoms ( e.g ., C ₁ -C ₁₅ alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (e.g., C ₁ -C ₁₃ alkyl). In certain embodiments, an alkyl comprises one to ten carbon atoms (e.g., C ₁ -C ₁₀ alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (e.g., Ci-Cs alkyl). In other embodiments, an alkyl comprises one to six carbon atoms (e.g., C ₁ -C ₆ alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (e.g., C ₁ -C ₅ alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (e.g., C ₁ -C ₄ alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (e.g., C ₁ -C ₃ alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (e.g., C ₁ -C ₂ alkyl). In other embodiments, an alkyl comprises one carbon atom (e.g., Ci alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (e.g., C ₅ -C ₁₅ alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (e.g., Cs-Cx alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (e.g., C ₂ -C ₅ alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (e.g., C ₃ -C ₅ alkyl). In other embodiments, the alkyl group is selected from methyl, ethyl, 1 -propyl (//-propyl), 1 -methyl ethyl (Ao-propyl), 1 -butyl (//-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (Ao-butyl), 1,1 -dimethyl ethyl (/e/7-butyl), and 1 -pentyl (//-pentyl). The alkyl is attached to the rest of the molecule by a single bond. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -0C(0)R ^a , -N(R ^a ) ₂ , -C(0)R ^a , -C(0)0R ^a , -C(0)N(R ^a ) ₂ , - N(R ^a )C(0)0R ^f , -0C(0)-NR ^a R ^f , -N(R ^a )C(0)R ^f , -N(R ^a )S(0) _t R ^f (where t is 1 or 2), -S(0) _t 0R ^a (where t is 1 or 2), -S(0) _t R ^f (where t is 1 or 2), and -S(0) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R ^f is independently alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

[0030] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above.

[0031] "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and having from two to twelve carbon atoms. In other embodiments, an alkenyl comprises two to ten carbon atoms. In certain embodiments, an alkenyl comprises two to eight carbon atoms. In other embodiments, an alkenyl comprises two to six carbon atoms. In other embodiments, an alkenyl comprises two to four carbon atoms. The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (z.e., vinyl), prop-l-enyl (z.e., allyl), but-l-enyl, pent-l-enyl, penta-l,4-dienyl, and the like. Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , - SR ^a , -OC(0)-R ^f , -N(R ^a ) ₂ , -C(0)R ^a , -C(0)OR ^a , -C(0)N(R ^a ) ₂ , -N(R ^a )C(0)OR ^f , -OC(O)- nR ^a R ^f , -N(R ^a )C(0)R ^f , -N(R ^a )S(0) _t R ^f (where t is 1 or 2), -S(0) _t OR ^a (where t is 1 or 2), -S(0) _t R ^f (where t is 1 or 2), and -S(0) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R ^f is independently alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

[0032] "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, having from two to twelve carbon atoms. In certain embodiments, an alkynyl comprises two to ten carbon atoms. In certain embodiments, an alkynyl comprises two to eight carbon atoms. In other embodiments, an alkynyl has two to four carbon atoms. The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(0)R ^a , -N(R ^a ) ₂ , -C(0)R ^a , -C(0)OR ^a , - C(0)N(R ^a ) ₂ , -N(R ^a )C(0)OR ^f , -OC(0)-NR ^a R ^f , -N(R ^a )C(0)R ^f , -N(R ^a )S(0) _t R ^f (where t is 1 or 2), - S(0) _t OR ^a (where t is 1 or 2), -S(0) _t R ^f (where t is 1 or 2), and -S(0) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R ^f is independently alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

[0033] "Aryl" refers to a radical derived from an aromatic monocyclic or multi cyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or multicyclic hydrocarbon ring system contains only hydrogen and carbon from six to eighteen carbon atoms, where at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) p-electron system in accordance with the Hiickel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals optionally substituted by one or more substituents independently selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -R ^b -OR ^a , -R ^b -0C(0)-R ^a , -R ^b -0C(0)-0R ^a , -R ^b -0C(0)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C (0)R ^a , -R ^b -C(0)0R ^a , -R ^b -C(0)N(R ^a ) ₂ , -R ^b -0-R ^c -C(0)N(R ^a ) ₂ , -R ^b -N(R ^a )C(0)0R ^a , -R ^b -N(R ^a )C( 0)R ^a , -R ^b -N(R ^a )S(0) _t R ^a (where t is 1 or 2), -R ^b -S(0) _t OR ^a (where t is 1 or 2), -R ^b -S(0) _t R ^a (where t is 1 or 2) and -R ^b -S(0) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted with one or more halo groups), aralkyl, heterocycloalkyl, heteroaryl or heteroarylalkyl, each R ^b is independently a direct bond or a straight or branched alkyl ene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain.

[0034] "Aryloxy" refers to a radical bonded through an oxygen atom of the formula -O-aryl, where aryl is as defined above.

[0035] "Aralkyl" refers to a radical of the formula -R ^c -aryl where R ^c is an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group.

[0036] " Aralkyloxy" refers to a radical bonded through an oxygen atom of the formula -O- aralkyl, where aralkyl is as defined above.

[0037] "Aralkenyl" refers to a radical of the formula -R ^d -aryl where R ^d is an alkenylene chain as defined above. The aryl part of the aralkenyl radical is optionally substituted as described above for an aryl group. The alkenylene chain part of the aralkenyl radical is optionally substituted as defined above for an alkenylene group. [0038] "Aralkynyl" refers to a radical of the formula -R ^e -aryl, where R ^e is an alkynylene chain as defined above. The aryl part of the aralkynyl radical is optionally substituted as described above for an aryl group. The alkynylene chain part of the aralkynyl radical is optionally substituted as defined above for an alkynylene chain.

[0039] "Cycloalkyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, having from three to fifteen carbon atoms. In certain embodiments, a cycloalkyl comprises three to ten carbon atoms. In other embodiments, a cycloalkyl comprises five to seven carbon atoms. The cycloalkyl is attached to the rest of the molecule by a single bond. Cycloalkyls are saturated, (i.e., containing single C-C bonds only) or partially unsaturated (i.e., containing one or more double bonds or triple bonds.) Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In certain embodiments, a cycloalkyl comprises three to eight carbon atoms (e.g., C ₃ -C ₈ cycloalkyl). In other embodiments, a cycloalkyl comprises three to seven carbon atoms (e.g., C3-C7 cycloalkyl). In other embodiments, a cycloalkyl comprises three to six carbon atoms (e.g., C3-C6 cycloalkyl). In other embodiments, a cycloalkyl comprises three to five carbon atoms (e.g., C3-C5 cycloalkyl). In other embodiments, a cycloalkyl comprises three to four carbon atoms (e.g., C3-C4 cycloalkyl). A partially unsaturated cycloalkyl is also referred to as "cycloalkenyl." Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbomyl (i.e., bicyclo[2.2.1]heptanyl), norbomenyl, decalinyl,

7, 7-dimethyl -bicyclo[2.2. l]heptanyl, and the like. Unless otherwise stated specifically in the specification, the term "cycloalkyl" is meant to include cycloalkyl radicals optionally substituted by one or more substituents independently selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -R ^b -OR ^a , -R ^b -OC(0)-R ^a , -R ^b -OC(0)-OR ^a , -R ^b -OC(0)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C (0)R ^a , -R ^b -C(0)OR ^a , -R ^b -C(0)N(R ^a ) ₂ , -R ^b -0-R ^c -C(0)N(R ^a ) ₂ , -R ^b -N(R ^a )C(0)OR ^a , -R ^b -N(R ^a )C( 0)R ^a , -R ^b -N(R ^a )S(0) _t R ^a (where t is 1 or 2), -R ^b -S(0) _t OR ^a (where t is 1 or 2), -R ^b -S(0) _t R ^a (where t is 1 or 2) and -R ^b -S(0) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted with one or more halo groups), aralkyl, heterocycloalkyl, heteroaryl or heteroarylalkyl, each R ^b is independently a direct bond or a straight or branched alkyl ene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain.

[0040] "Halo" or "halogen" refers to bromo, chloro, fluoro, or iodo substituents. [0041] "Haloalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above.

[0042] "Fluoroalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more fluoro radicals, as defined above, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, l-fluoromethyl-2-fluoroethyl, and the like. The alkyl part of the fluoroalkyl radical are optionally substituted as defined above for an alkyl group.

[0043] "Haloalkoxy" refers to an alkoxy radical, as defined above, that is substituted by one or more halo radicals, as defined above.

[0044] "Heterocycloalkyl" refers to a stable 3- to 18-membered non-aromatic ring radical that comprises two to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen, and sulfur. Unless stated otherwise specifically in the specification, the heterocycloalkyl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which include fused, spiro, or bridged ring systems. The heteroatoms in the heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quatemized. The heterocycloalkyl radical is partially or fully saturated. In some embodiments, the heterocycloalkyl is attached to the rest of the molecule through any atom of the ring(s).

Examples of such heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1 -oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise specifically in the specification, the term "heterocycloalkyl" is meant to include heterocycloalkyl radicals as defined above that are optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -R ^b -OR ^a , -R ^b -OC(0)-R ^a , -R ^b -OC(0)-OR ^a , -R ^b -OC(0)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C (0)R ^a , -R ^b -C(0)OR ^a , -R ^b -C(0)N(R ^a ) ₂ , -R ^b -0-R ^c -C(0)N(R ^a ) ₂ , -R ^b -N(R ^a )C(0)OR ^a , -R ^b -N(R ^a )C( 0)R ^a , -R ^b -N(R ^a )S(0) _t R ^a (where t is 1 or 2), -R ^b -S(0) _t OR ^a (where t is 1 or 2), -R ^b -S(0) _t R ^a (where t is 1 or 2) and -R ^b -S(0) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl or heteroarylalkyl, each R ^b is independently a direct bond or a straight or branched alkylene or alkenyl ene chain, and R ^c is a straight or branched alkylene or alkenylene chain. [0045] "Heteroaryl" refers to a radical derived from a 5- to 18-membered aromatic ring radical that comprises one to seventeen carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, the heteroaryl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, wherein at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) p-electron system in accordance with the Hiickel theory. Heteroaryl includes fused or bridged ring systems. The heteroatom(s) in the heteroaryl radical is optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl is attached to the rest of the molecule through any atom of the ring(s). Unless stated otherwise specifically in the specification, the term "heteroaryl" is meant to include heteroaryl radicals as defined above that are optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo, haloalkyl, oxo, thioxo, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroaryl alkyl, -R ^b -OR ^a , -R ^b -0C(0)-R ^a , -R ^b -0C(0)-0R ^a , -R ^b -0C(0)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C(0)R ^a , -R ^b -C(0)0R ^a , -R ^b - C(0)N(R ^a ) ₂ , -R ^b -0-R ^c -C(0)N(R ^a ) ₂ , -R ^b -N(R ^a )C(0)0R ^a , -R ^b -N(R ^a )C(0)R ^a , -R ^b -N(R ^a )S(0) _t R ^a (where t is 1 or 2), -R ^b -S(0) _t OR ^a (where t is 1 or 2), -R ^b -S(0) _t R ^a (where t is 1 or 2) and -R ^b - S(0) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroaryl alkyl, each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain.

[0046] "A-heteroaryl" refers to a heteroaryl radical as defined above containing at least one nitrogen and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a nitrogen atom in the heteroaryl radical. An N-heteroaryl radical is optionally substituted as described above for heteroaryl radicals.

[0047] "C -heteroaryl" refers to a heteroaryl radical as defined above and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a carbon atom in the heteroaryl radical. A C-heteroaryl radical is optionally substituted as described above for heteroaryl radicals.

[0048] "Heteroaryloxy" refers to radical bonded through an oxygen atom of the formula -O- heteroaryl, where heteroaryl is as defined above.

[0049] "Heteroarylalkyl" refers to a radical of the formula -R ^c -heteroaryl, where R ^c is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkyl radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkyl radical is optionally substituted as defined above for a heteroaryl group. [0050] "Heteroarylalkoxy" refers to a radical bonded through an oxygen atom of the formula - 0-R ^c -heteroaryl, where R ^c is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkoxy radical is optionally substituted as defined above for a heteroaryl group.

[0051] A "tautomer" refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. In certain embodiments, the compounds presented herein exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibrium include:

[0052] "Optional" or "optionally" means that a subsequently described event or circumstance may or may not occur and that the description includes instances when the event or circumstance occurs and instances in which it does not. The term “optionally substituted” or “substituted” means that the referenced group may be substituted with one or more additional group(s) individually and independently selected from alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, -OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, -CN, alkyne, Ci-C ₆ alkylalkyne, halo, acyl, acyloxy, -CO2H, -CO2- alkyl, nitro, haloalkyl, fluoroalkyl, and amino, including mono- and di -substituted amino groups (e.g. -NH2, -NHR, -N(R) ₂ ), and the protected derivatives thereof. By way of example, an optional substituent may be L ^S R ^S , wherein each L ^s is independently selected from a bond, -0-, - C(=0)-, -S-, -S(=0)-, -S(=0) ₂ -, -NH-, -NHC(O)-, -C(0)NH-, S(=0) ₂ NH-, -NHS(=0) ₂ , - 0C(0)NH-, -NHC(0)0-, -(Ci-Cealkyl)-, or -(C2-C6alkenyl)-; and each R ^s is independently selected from among H, (Ci-C ₆ alkyl), (Cri-Cxcycloalkyl), aryl, heteroaryl, and heterocycloalkyl. [0053] "Pharmaceutically acceptable salt" includes both acid and base addition salts. A pharmaceutically acceptable salt of any one of the compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0054] "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts that are formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc. and include, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, / oluenesulfonic acid, salicylic acid, and the like. Exemplary salts thus include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinate suberates, sebacates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, and the like. Also contemplated are salts of amino acids, such as arginates, gluconates, and galacturonates (see, for example, Berge S.M. et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1-19 (1997)). Acid addition salts of basic compounds are prepared by contacting the free base forms with a sufficient amount of the desired acid to produce the salt.

[0055] "Pharmaceutically acceptable base addition salt" refers to those salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. In some embodiments, pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, A/ A'-dibenzyl ethyl enedi ami ne, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N- methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine,

A -ethyl pi peri dine, polyamine resins, and the like. See Berge et al., supra.

[0056] As used herein, "treatment" or "treating" or "palliating" or "ameliorating" are used interchangeably herein. These terms refer to an approach for obtaining beneficial or desired results including, but not limited to, therapeutic benefit and/or a prophylactic benefit. By "therapeutic benefit" is meant eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient is still afflicted with the underlying disorder. For prophylactic benefit, the compositions are administered to a patient at risk of developing a particular disease, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease has not been made.

[0057] A “prodrug” refers to an agent that is converted into the parent drug in vivo. Prodrugs are often useful because, in some situations, they are easier to administer than the parent drug. They are, for instance, bioavailable by oral administration whereas the parent is not. The prodrug may be a substrate for a transporter. Further or alternatively, the prodrug also has improved solubility in pharmaceutical compositions over the parent drug. In some embodiments, the design of a prodrug increases the effective water solubility. An example, without limitation, of a prodrug is a compound described herein, which is administered as an phosphonooxymethyl derivative (the “prodrug”), but then is metabolically hydrolyzed to provide the active entity. In certain embodiments, upon in vivo administration, a prodrug is chemically converted to the biologically, pharmaceutically or therapeutically active form of the compound. In certain embodiments, a prodrug is enzymatically metabolized by one or more steps or processes to the biologically, pharmaceutically or therapeutically active form of the compound. In some embodiments, compounds described herein are cleaved by an esterase. In some embodiments, compounds described herein are cleaved by a phosphatase.

[0058] Prodrugs described herein include, but are not limited to, esters, ethers, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl derivatives, quaternary derivatives of tertiary amines, N-Mannich bases, Schiff bases, amino acid conjugates, phosphate esters, sulfonamides, amides, phosphoramidates and sulfonate esters. See for example Design of Prodrugs, Bundgaard, A. Ed., Elseview, 1985 and Method in Enzymology, Widder, K. et al. , Ed.; Academic, 1985, vol. 42, p. 309-396; Bundgaard, H. “Design and Application of Prodrugs” in A Textbook of Drug Design and Development, Krosgaard -Larsen and H. Bundgaard, Ed., 1991, Chapter 5, p. 113-191; and Bundgaard, H., Advanced Drug Delivery Review, 1992, 8, 1-38, each of which is incorporated herein by reference.

Compounds

(IXa), (IXb), (X), (Xa), or (Xb) described herein are prodrugs of ALOX-15 inhibitors. In some embodiments, the compounds of Formula (I), (la), (lb), (II), (Ha), (lib), (III), (Ilia), (Illb), (IV),

(IX), (IXa), (IXb), (X), (Xa), or (Xb) described herein, and pharmaceutical compositions comprising these compounds, are useful for the treatment of an eosinophilic airway disease including, but not limited to, asthma, chronic rhinosinusitis, nasal polyposis and allergic rhinitis. In some embodiments, the compounds of Formula (I), (la), (lb), (II), (Ha), (lib), (III), (Ilia),

(Villa), (Vlllb), (IX), (IXa), (IXb), (X), (Xa), or (Xb) described herein, and pharmaceutical compositions comprising these compounds, are useful for the treatment of an eosinophilic disease of the gastro-intestinal tract including, but not limited to, eosinophilic esophagitis and eosinophilic gastritis.

[0060] In some embodiments is a compound of Formula (I):

Ring A is selected from C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and C2-9heteroaryl; Ring B is selected from C2-9heterocycloalkyl and C2-9heteroaryl; R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - R ¹¹ , - Ci_ 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; eac N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; n is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0061] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -P(0)(OH) _2.

[0062] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(R ⁵ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is Ci^alkyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- 6alkyl-N(R ¹⁰ )2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- 6alkyl-NH2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- 6alkyl-N(H)CH3. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-6alkyl-N(R ¹⁰ )2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-ealkyl-NFh. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- ₆ alkyl-N(H)CH _3.

[0063] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is Ring A is C _2-9 heteroaryl. In some embodiments is a compound of ceutically acceptable salt or solvate thereof, wherein R ¹ is Ring A is C _2-9 heteroaryl selected from oxazolyl, thiazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C ₂ - cheteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl. [0064] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[0065] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci^alkyl.

[0066] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is Ring B is C2-9heteroaryl. In some embodiments is a compound of maceutically acceptable salt or solvate thereof, wherein R ¹ is Ring B is C2-9heteroaryl selected from pyrazolyl, pyrrolyl, and imidazolyl.

[0067] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2-9heterocycloalkyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2-9heterocycloalkyl selected from pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl.

[0068] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0.

[0069] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0, 1, 2, or 3. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0, 1, or 2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 3. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 1. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0.

[0070] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein q is 0, 1, 2, or 3. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein q is 0, 1, or 2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein q is 3. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein q is 2. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein q is 1. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein q is 0.

[0071] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci^alkyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is unsubstituted Ci- ₆ alkyl.

[0072] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁶ and R ¹⁷ are each independently selected from halogen, -CN, Ci- ₆ alkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, -OR ⁶ , -SR ⁶ , -N(R ⁶ )2, -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , - 0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , -N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , - S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, Cs-ecycloalkyl, and C ₂ - 9heterocycloalkyl are optionally substituted with one, two, or three R ⁹ In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁶ and R ¹⁷ are each independently selected from halogen and Ci- ₆ alkyl optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁶ and R ¹⁷ are each independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁶ and R ¹⁷ are each independently selected from halogen. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁶ and R ¹⁷ are each independently selected from -F, -Cl, or -Br. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein q is 0. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p and q are 0.

[0073] In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF.

[0074] In some embodiments is a compound of Formula (I) having the structure of Formula (la): Formula (la); wherein:

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; or a pharmaceutically acceptable salt or solvate thereof.

In some embodiments is a compound of Formula (la), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (la), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (la), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF.

[0075] In some embodiments is a compound of Formula (I) having the structure of Formula (lb): wherein:

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and C _2-9 heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci^haloalkyl;

R ³ is selected from Ci-6alkyl or -Ci- ₆ alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and - 0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci^haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl, wherein Ci- ₆ alkyl, C2-6alkenyl, C2- 6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci-9heteroaryl, - OR ¹¹ , -SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci_ 6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, -Ci- ₆ alkyl-C ₆ - loaryl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci^alkyl, Ci- ₆ haloalkyl, Ci- ealkoxy, Ci- ₆ haloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , - C(0)C(0)N(R ^u ) ₂ , -0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , - N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6alkenyl, C2- 6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci- ₆ alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci- ₆ alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[0076] In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-9heteroaryl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2- 9heteroaryl selected from oxazolyl, thiazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-9heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl.

[0077] In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[0078] In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is Ci^alkyl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is -Ci-6alkyl-N(R ¹⁰ )2.

In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is -Ci-ealkyl-NFh. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is -Ci-6alkyl-N(H)CH3. [0079] In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci^alkyl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is -CFF. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is H.

[0080] In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0.

[0081] In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci^alkyl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is i and R ⁴ is unsubstituted Ci- ₆ alkyl.

[0082] In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (lb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF. [0083] In some embodiments is a compound of Formula (II):

Formula (II); wherein:

X is a bond, Ci-6alkyl, C _2-6 alkenyl, or C _2-6 alkynyl;

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and C _2-9 heteroaryl;

Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3- 6cycloalkyl, C2-9heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ¹¹ , - SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci_ 6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; eac wherein Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁷ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, or Ci. 9heteroaryl, wherein C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) ₂ ; n is 0, 1, 2, 3, or 4; and p is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof. [0084] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond, Ci^alkyl, or C2-6alkenyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond or Ci- ₆ alkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is Ci- ₆ alkyl.

[0085] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -P(0)(OH) _2.

[0086] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(R ⁵ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is Ci^alkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- 6alkyl-N(R ¹⁰ )2. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- 6alkyl-NH2. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- 6alkyl-N(H)CH3. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-6alkyl-N(R ¹⁰ )2. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-ealkyl-NFh. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- ₆ alkyl-N(H)CH _3.

[0087] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is Ring A is C2-9heteroaryl. In some embodiments is a compound of aceutically acceptable salt or solvate thereof, wherein R ¹ is Ring A is C2-9heteroaryl selected from oxazolyl, thiazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-

9heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl.

[0088] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[0089] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci^alkyl. [0090] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is Ring B is C2-9heteroaryl. In some embodiments is a compound of maceutically acceptable salt or solvate thereof, wherein R ¹ is Ring B is C2-9heteroaryl selected from pyrazolyl, pyrrolyl, and imidazolyl.

[0091] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2-9heterocycloalkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2-9heterocycloalkyl selected from pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl. [0092] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0.

[0093] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0, 1, 2, or 3. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0, 1, or 2. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 3. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 2. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 1. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0.

[0094] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is unsubstituted Ci- ₆ alkyl.

[0095] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, each R ¹⁶ is independently selected from halogen, -CN, Ci- ₆ alkyl, C3- ecycloalkyl, C _2.9 heterocycloalkyl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , -N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , - S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -OC(0)R ⁸ , wherein Ci- ₆ alkyl, C3-6cycloalkyl, and C ₂ . iheterocycloalkyl, are optionally substituted with one, two, or three R ⁹ In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ¹⁶ is independently selected from halogen and Ci- ₆ alkyl optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ¹⁶ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ¹⁶ is independently selected from halogen. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ¹⁶ are each independently selected from -F, -Cl, or -Br. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0.

[0096] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C ₆ -ioaryl, or Ci- iheteroaryl, wherein C ₆ -ioaryl and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is -C(0)OR ⁶ , -C(0)R ⁸ , C ₆ -ioaryl, or Ci-cheteroaryl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is Ci-9heteroaryl, wherein Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is selected from benzothiophenyl, benzofuranyl, indolyl, benzimidazolyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, benzooxazolyl, and benzoisoxazolyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is selected from benzothiophenyl, benzofuranyl, benzooxazolyl, and benzoisoxazolyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is benzothiophenyl or benzofuranyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci- 9heteroaryl is benzofuranyl.

[0097] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , - S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -S(0) ₂ R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , or N(R ⁷ )C(0)R ⁸ . In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -N(R ⁷ )S(0) ₂ R ⁸ .

[0098] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CH _3.

[0099] In some embodiments is a compound of Formula (II) having the structure of Formula

(Ha): Formula (Ha); wherein:

X is a bond, Ci^alkyl, C _2-6 alkenyl, or C _2-6 alkynyl;

R ² is selected from H, Ci- ₆ alkyl, and Ci^haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, - OR ¹¹ , -SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ - loaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci- ₆ alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci- ₆ alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl;

R ¹⁷ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, or Ci- ₉ heteroaryl, wherein C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- 9heteroaryl are optionally substituted with one, two, or three R ⁹ ; and R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) ₂ ; or a pharmaceutically acceptable salt or solvate thereof.

[00100] In some embodiments is a compound of Formula (Ha), or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond, Ci- ₆ alkyl, or C ₂ ^alkenyl. In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond or Ci- ₆ alkyl. In some embodiments is a compound of Formula (Ha), or a pharmaceutically acceptable salt or solvate thereof, wherein X is Ci^alkyl.

[00101] In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C ₆ -ioaryl, or Ci- ₉ heteroaryl, wherein C ₆ -ioaryl and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is -C(0)OR ⁶ , -C(0)R ⁸ , C ₆ -ioaryl, or Ci- ₉ heteroaryl. In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci- ₉ heteroaryl. In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci- ₉ heteroaryl, wherein C ₆ -ioaryl and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is Ci- ₉ heteroaryl, wherein Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci- ₉ heteroaryl is benzothiophenyl, benzofuranyl, indolyl, benzimidazolyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, benzooxazolyl, or benzoisoxazolyl. In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci- ₉ heteroaryl is benzothiophenyl, benzofuranyl, benzooxazolyl, or benzoisoxazolyl. In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-cheteroaryl is benzothiophenyl or benzofuranyl. In some embodiments is a compound of Formula (Ha), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is benzofuranyl.

[00102] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , - S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ . In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -S(0) ₂ R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , or N(R ⁷ )C(0)R ⁸ . In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -N(R ⁷ )S(0) ₂ R ⁸ .

[00103] In some embodiments is a compound of Formula (Ha), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (Ila), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFR

[00104] In some embodiments is a compound of Formula (II) having the structure of Formula

(lib):

Formula (lib); wherein:

Ring A is selected from C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and C2-9heteroaryl; X is a bond, Ci^alkyl, C2-6alkenyl, or C2-6alkynyl;

R ² is selected from H, Ci- ₆ alkyl, and Ci^haloalkyl;

R ³ is selected from Ci-6alkyl or -Ci-6alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ )2, - C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and - OC(0)R ⁸ , wherein Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- cheterocydoalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, - OR ¹¹ , -SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C2- ₆ alkenyl, C2- ₆ alkynyl, C ₃ - ₆ cycloalkyl, C2- ₉ heterocycloalkyl, -Ci- ₆ alkyl-C ₆ - loaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci- ₆ alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci- ₆ alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl;

R ¹⁷ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, or Ci- ₉ heteroaryl, wherein C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- 9heteroaryl are optionally substituted with one, two, or three R ⁹ ; R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) ₂ ; n is 0, 1, 2, 3, or 4; and p is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[00105] In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C ₂ -9heteroaryl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C ₂ -9heteroaryl selected from oxazolyl, thiazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C ₂ -9heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl.

[00106] In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[00107] In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci- ₆ alkyl.

[00108] In some embodiments is a compound of Formula (Hb), or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond, Ci- ₆ alkyl, or C ₂ ^alkenyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond or Ci- ₆ alkyl. In some embodiments is a compound of Formula (Hb), or a pharmaceutically acceptable salt or solvate thereof, wherein X is Ci^alkyl.

[00109] In some embodiments is a compound of Formula (Hb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ . In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is -Ci- ₆ alkyl-NH ₂ . In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³ is -Ci. ₆ alkyl-N(H)CH .

[00110] In some embodiments is a compound of Formula (Hb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is -CFf.

In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is H. [00111] In some embodiments is a compound of Formula (Hb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0.

[00112] In some embodiments is a compound of Formula (Hb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci^alkyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is unsubstituted Ci- ₆ alkyl.

[00113] In some embodiments is a compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is -C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C ₆ -ioaryl, or Ci- iheteroaryl, wherein C ₆ -ioaryl and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is -C(0)OR ⁶ , -C(0)R ⁸ , C ₆ -ioaryl, or Ci- iheteroaryl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is Ci- 9heteroaryl, wherein Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is benzothiophenyl, benzofuranyl, indolyl, benzimidazolyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, benzooxazolyl, or benzoisoxazolyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is benzothiophenyl, benzofuranyl, benzooxazolyl, or benzoisoxazolyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is benzothiophenyl or benzofuranyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein Ci-9heteroaryl is benzofuranyl.

[00114] In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , - N(R ⁷ )S(0) ₂ R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) _2. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -S(0) ₂ R ⁸ , - N(R ⁷ )S(0) ₂ R ⁸ , or N(R ⁷ )C(0)R ⁸ . In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -N(R ⁷ )S(0) ₂ R ⁸ .

[00115] In some embodiments is a compound of Formula (Hb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (lib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF.

[00116] In some embodiments is a compound of Formula (III):

Ring A is selected from C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and C ₂ -9heteroaryl;

Ring B is selected from C ₂ -9heterocycloalkyl and C ₂ -9heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3- 6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)OR ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -OC(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - ryl, -OR ¹¹ , - )R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci^haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl;

R ¹⁶ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ ;

R ¹⁷ is C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, or Ci- ₉ heteroaryl, wherein C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[00117] In some embodiments is a compound of Formula (PI), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -P(0)(OH) _2.

[00118] In some embodiments is a compound of Formula (PI), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(R ⁵ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is - C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is - C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-6alkyl-N(R ¹⁰ )2. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-ealkyl-NFF. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-6alkyl-N(H)CH3. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- OC(0)R ³ and R ³ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- OC(0)R ³ and R ³ is -Ci-6alkyl-N(R ¹⁰ )2. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- OC(0)R ³ and R ³ is -Ci-ealkyl-NFh. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- OC(0)R ³ and R ³ is -Ci- ₆ alkyl-N(H)CH _.

[00119] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ , , , furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-

9heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl.

[00120] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[00121] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci- ₆ alkyl. [00122] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ Ring B is C2-9heteroaryl. In some embodiments is a compound of aceutically acceptable salt or solvate thereof, wherein R ¹ is ing B is C2-9heteroaryl selected from pyrazolyl, pyrrolyl, and imidazolyl.

[00123] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2-

9heterocycloalkyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2-

9heterocycloalkyl selected from pyrrolidinyl, piped dinyl, morpholinyl, and piperazinyl. [00124] In some embodiments is a compound of Formula (PI), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0.

[00125] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci^alkyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is unsubstituted Ci- ₆ alkyl.

[00126] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)OR ⁶ , -C(0)R ⁸ , or -S(0) ₂ R ⁸ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)OR ⁶ or -C(0)R ⁸ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is C ₆ -ioaryl or Ci-cheteroaryl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl or Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is phenyl.

[00127] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C2-9heterocycloalkyl, C ₆ -ioaryl, or Ci- 9heteroaryl, wherein C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl. In some embodiments is a compound of Formula (PI), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl, wherein C ₆ -ioaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein Ce- ioaryl is phenyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three halo or Ci^alkyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three halo, wherein halo is -F, -Cl, or -Br.

[00128] In some embodiments is a compound of Formula (PI), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) ₂ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)OR ⁶ , -C(0)R ⁸ , or -S(0) ₂ R ⁸ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo or Ci- ₆ alkyl. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo, wherein halo is -F, -Cl, or -Br.

[00129] In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl.

In some embodiments is a compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF.

[00130] In some embodiments is a compound of Formula (III) having the structure of Formula (Ilia):

Formula (Ilia); wherein:

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -

OR ¹¹ , -SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci-

₆ alkyl, C2- ₆ alkenyl, C2- ₆ alkynyl, C ₃ - ₆ cycloalkyl, C2- ₉ heterocycloalkyl, -Ci- ₆ alkyl-C ₆ - loaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci- ₆ alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci- ₆ alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl;

R ¹⁶ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ ;

R ¹⁷ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, or Ci-9heteroaryl, wherein C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci. 9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) ₂ ; or a pharmaceutically acceptable salt or solvate thereof.

[00131] In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)0R ⁶ , -C(0)R ⁸ , or -S(0) ₂ R ⁸ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)0R ⁶ or -C(0)R ⁸ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is C ₆ -ioaryl or Ci-9heteroaryl. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl or Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is phenyl.

[00132] In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C2-9heterocycloalkyl, C ₆ -ioaryl, or Ci- 9heteroaryl, wherein C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl, wherein C ₆ -ioaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein C ₆ -ioaryl is phenyl. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three halo or Ci- ₆ alkyl. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three halo, wherein halo is -F, -Cl, or -Br.

[00133] In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) _2. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)0R ⁶ , -C(0)R ⁸ , or -S(0) ₂ R ⁸ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo or Ci- ₆ alkyl. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo, wherein halo is -F, -Cl, or -Br.

[00134] In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci^alkyl. In some embodiments is a compound of Formula (Ilia), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF.

[00135] In some embodiments is a compound of Formula (III) having the structure of Formula (Bib): Formula (Illb); wherein:

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and C _2-9 heteroaryl;

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and - 0C(0)R ⁸ , wherein Ci. ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci^haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, - OR ¹¹ , -SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci_

6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, -Ci-6alkyl-C6- loaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6alkenyl, C2- 6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci- ₆ alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci- ₆ alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl;

R ¹⁶ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ ;

R ¹⁷ is C3-6cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, or Ci-9heteroaryl, wherein C3-

₆ cycloalkyl, C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or -S(0) ₂ N(R ⁶ ) ₂ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[00136] In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-9heteroaryl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-9heteroaryl selected from oxazolyl, thiazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-9heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl.

[00137] In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[00138] In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci- ₆ alkyl.

[00139] In some embodiments is a compound of Formula (nib), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0. [00140] In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci^alkyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is unsubstituted Ci- ₆ alkyl.

[00141] In some embodiments is a compound of Formula (Rib), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)OR ⁶ , -C(0)R ⁸ , or -S(0) ₂ R ⁸ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)OR ⁶ or -C(0)R ⁸ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is C ₆ -ioaryl or Ci-9heteroaryl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl or Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is selected from is -C(0)R ⁸ , wherein R ⁸ is phenyl.

[00142] In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C2-9heterocycloalkyl, C ₆ -ioaryl, or Ci- 9heteroaryl, wherein C2-9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl. In some embodiments is a compound of Formula (Rib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl or Ci-9heteroaryl, wherein C ₆ -ioaryl and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is C ₆ -ioaryl, wherein C ₆ -ioaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein C ₆ -ioaryl is phenyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three halo or Ci- ₆ alkyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁷ is phenyl, wherein the phenyl is optionally substituted with one, two, or three halo, wherein halo is -F, -Cl, or -Br.

[00143] In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)N(R ⁶ ) ₂ , -C(0)R ⁸ , -S(0) ₂ R ⁸ , or - S(0) ₂ N(R ⁶ ) _2. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)0R ⁶ , -C(0)R ⁸ , or -S(0) ₂ R ⁸ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo or Ci- ₆ alkyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is -C(0)R ⁸ , wherein R ⁸ is phenyl optionally substituted with one, two, or three halo, wherein halo is -F, -Cl, or -Br.

[00144] In some embodiments is a compound of Formula (Rib), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (Illb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF.

[00145] In some embodiments is a compound of Formula (IV):

Formula (IV); wherein:

Ring A is selected from C3- ₆ cycloalkyl, C2- ₉ heterocycloalkyl, C ₆ -ioaryl, and C2- ₉ heteroaryl; Ring B is selected from C _2-9 heterocycloalkyl and C _2-9 heteroaryl;

R ² is selected from H, Ci. ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ )2; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - 6cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ¹¹ , - ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci-

₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci^alkyl-C ₆ -ioaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ci- ₆ alkoxy, Ci- ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , -C(0)C(0)N(R ^u ) ₂ , - 0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , -N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^u ) ₂ , and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci^alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C _2.

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci^alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2.6 alkenyl, C _2.6 alkynyl, C3-6cycloalkyl, C _2.

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl;

R ¹⁶ and R ¹⁷ are independently selected from H, halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _{2. 6} alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, Ci-9heteroaryl, -OR ⁶ , -SR ⁶ , - N(R ⁶ ) ₂ , -C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and -0C(0)R ⁸ , wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ¹⁸ is Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C _2. 9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R ⁹ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[00146] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -P(0)(OH) _2.

[00147] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(R ⁵ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is - C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is - C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- ₆ alkyl-N(R ¹⁰ ) _2. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci- ₆ alkyl-NH _2. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(H)C _2-6 alkyl-0C(0)R ³ and R ³ is -Ci-6alkyl-N(H)CH3. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl-0C(0)R ³ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- 0C(0)R ³ and R ³ is Ci- ₆ alkyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- 0C(0)R ³ and R ³ is -Ci-6alkyl-N(R ¹⁰ )2. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- 0C(0)R ³ and R ³ is -Ci-ealkyl-NFfc. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is -C(0)N(CH ₃ )C _2-6 alkyl- 0C(0)R ³ and R ³ is -Ci- ₆ alkyl-N(H)CH _.

[00148] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ , , , furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C2-

9heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl.

[00149] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[00150] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci-6alkyl.

[00151] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ Ring B is C2-9heteroaryl. In some embodiments is a compound of

Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is Ring B is C2-9heteroaryl selected from pyrazolyl, pyrrolyl, and imidazolyl.

[00152] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2- iheterocycloalkyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is C2- iheterocycloalkyl selected from pyrrolidinyl, piped dinyl, morpholinyl, and piperazinyl. [00153] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0.

[00154] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci^alkyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is unsubstituted Ci- ₆ alkyl. [00155] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ and R ¹⁷ are independently selected from H, halogen, Ci- ₆ alkyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , -C(0)0R ⁶ , wherein Ci- ₆ alkyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are unsubstituted. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ and R ¹⁷ are independently selected from H, halogen, Ci- ₆ alkyl, C ₃ - ₆ cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , -C(0)0R ⁶ , wherein Ci- ₆ alkyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ and R ¹⁷ are independently selected from H, halogen, or Ci^alkyl, wherein Ci- ₆ alkyl is unsubstituted. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ and R ¹⁷ are independently selected from H, halogen, or Ci- ₆ alkyl, wherein Ci- ₆ alkyl is optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ is H. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁷ is H. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, R ¹⁶ and R ¹⁷ are H.

[00156] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - ₆ cycloalkyl, C _2-9 heterocycloalkyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is selected from Ci^alkyl, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, and C _2-9 heterocycloalkyl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, and C _3-6 cycloalkyl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl or C _2-6 alkenyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl or C _2-6 alkenyl, wherein Ci- ₆ alkyl and C _2-6 alkenyl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci^alkyl, wherein Ci- ₆ alkyl is optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is C _2-6 alkenyl, wherein C ₂ - ₆ alkenyl is optionally substituted with one, two, or three R ⁹ .

[00157] In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CFF.

[00158] In some embodiments is a compound of Formula (IV) having the structure of Formula

(IVa):

Formula (IVa); wherein:

R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci-9heteroaryl, - OR ¹¹ , -SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C ₂ -6alkenyl, C ₂ -6alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, -Ci-6alkyl-C6- loaryl, C ₆ -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci^alkyl, Ci- ₆ haloalkyl, Ci- ealkoxy, Ci-ehaloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , - C(0)C(0)N(R ^u ) ₂ , -0C(0)N(R ⁿ ) _¾ -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , - N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^u ) ₂ , and -0C(0)R ¹³ ; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C ₂ .

₆ alkynyl, C3-6cycloalkyl, C ₂ -9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹² is independently selected from H and Ci- ₆ alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ ^alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl; each R ¹⁴ is independently selected from H and Ci- ₆ alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ ^alkynyl, C3-6cycloalkyl, C ₂ .

9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl;

R ¹⁸ is Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ .9heterocycloalkyl, C ₆ -ioaryl, and Ci-9heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C3-6cycloalkyl, C ₂ . cheterocydoalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; or a pharmaceutically acceptable salt or solvate thereof.

[00159] In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - ₆ cycloalkyl, or C _2-9 heterocycloalkyl. In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, and C _3-6 cycloalkyl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl or C _2-6 alkenyl. In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl or C _2-6 alkenyl, wherein Ci- ₆ alkyl and C _2-6 alkenyl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl, wherein Ci- ₆ alkyl is optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is C _2-6 alkenyl, wherein C _2-6 alkenyl is optionally substituted with one, two, or three R ⁹ .

[00160] In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is H. In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is Ci- ₆ alkyl. In some embodiments is a compound of Formula (IVa), or a pharmaceutically acceptable salt or solvate thereof, wherein R ² is -CH _3.

[00161] In some embodiments is a compound of Formula (IV) having the structure of Formula (IVb):

Formula (IVb); wherein:

Ring A is selected from C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C6-ioaryl, and C _2-9 heteroaryl; R ² is selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl;

R ³ is selected from Ci- ₆ alkyl or -Ci- ₆ alkyl-N(R ¹⁰ ) ₂ ; each R ⁴ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, Ci- ₉ heteroaryl, -OR ⁶ , -SR ⁶ , -N(R ⁶ ) ₂ , - C(0)0R ⁶ , -C(0)N(R ⁶ ) ₂ , -0C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)N(R ⁶ ) ₂ , -N(R ⁷ )C(0)0R ⁶ , - N(R ⁷ )C(0)R ⁸ , -N(R ⁷ )S(0) ₂ R ⁸ , -C(0)R ⁸ , -S(0)R ⁸ , -S(0) ₂ R ⁸ , -S(0) ₂ N(R ⁶ ) ₂ , and - 0C(0)R ⁸ , wherein Ci. ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ;

R ⁵ is selected from H, Ci- ₆ alkyl, and Ci^haloalkyl; each R ⁶ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C ₂ - 6alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁷ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ⁸ is independently selected from Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; each R ⁹ is independently selected from halogen, -CN, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, -Ci- ₆ alkyl-C ₆ -ioaryl, C ₆ -ioaryl, Ci- ₉ heteroaryl, - OR ¹¹ , -SR ¹¹ , -N(R ¹² )(R ¹³ ), -C(0)0R ¹² , -C(0)N(R ¹² )(R ¹³ ), -C(0)C(0)N(R ¹² )(R ¹³ ), - 0C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)N(R ¹² )(R ¹³ ), -N(R ¹⁴ )C(0)0R ¹⁵ , -N(R ¹⁴ )C(0)R ¹⁵ , - N(R ¹⁴ )S(0) ₂ R ¹⁵ , -C(0)R ¹⁵ , -S(0) ₂ R ¹⁵ , -S(0) ₂ N(R ¹² )(R ¹³ ), and -0C(0)R ¹⁵ , wherein Ci- 6alkyl, C2- ₆ alkenyl, C2- ₆ alkynyl, C ₃ - ₆ cycloalkyl, C2- ₉ heterocycloalkyl, -Ci- ₆ alkyl-C ₆ - loaryl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci^alkyl, Ci- ₆ haloalkyl, Ci. ealkoxy, Ci- ₆ haloalkoxy, -OR ¹¹ , -SR ¹¹ , -N(R ^U ) ₂ , -C(0)0R ^u , -C(0)N(R ^u ) ₂ , - C(0)C(0)N(R ^u ) ₂ , -0C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)N(R ^u ) ₂ , -N(R ¹² )C(0)0R ^u , - N(R ¹² )C(0)R ¹³ , -N(R ¹² )S(0) ₂ R ¹³ , -C(0)R ¹³ , -S(0) ₂ R ¹³ , -S(0) ₂ N(R ^U )2, and -0C(0)R ¹³ ; each R ¹⁰ is independently selected from H, Ci- ₆ alkyl, and Ci- ₆ haloalkyl; each R ¹¹ is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C ₂ - 6alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹² is independently selected from H and Ci- ₆ alkyl; each R ¹³ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl; each R ¹⁴ is independently selected from H and Ci- ₆ alkyl; each R ¹⁵ is selected from Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl;

R ¹⁸ is Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C ₂ - 9heterocycloalkyl, C ₆ -ioaryl, and Ci- ₉ heteroaryl are optionally substituted with one, two, or three R ⁹ ; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt or solvate thereof.

[00162] In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C _2-9 heteroaryl. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C _2-9 heteroaryl selected from oxazolyl, thiazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is C _2-9 heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is pyridinyl.

[00163] In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is phenyl.

[00164] In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is Ci- ₆ alkyl.

[00165] In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, or 2. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0.

[00166] In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R ⁴ is independently selected from halogen and unsubstituted Ci- ₆ alkyl. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R ⁴ is independently selected from halogen and unsubstituted Ci^alkyl. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is halogen. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R ⁴ is unsubstituted Ci- ₆ alkyl.

[00167] In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci^alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ - ₆ cycloalkyl, C _2-9 heterocycloalkyl. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C _3-6 cycloalkyl, C _2-9 heterocycloalkyl, wherein Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, and C _3-6 cycloalkyl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl or C _2-6 alkenyl. In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl or C _2-6 alkenyl, wherein Ci- ₆ alkyl and C _2-6 alkenyl are optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is Ci- ₆ alkyl, wherein Ci- ₆ alkyl is optionally substituted with one, two, or three R ⁹ . In some embodiments is a compound of Formula (IVb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹⁸ is C _2-6 alkenyl, wherein C _2-6 alkenyl is optionally substituted with one, two, or three R ⁹ .