Certain chemical compositions and methods of use thereof

1. A compound of Formula (I-A):

or a pharmaceutically acceptable salt thereof,

wherein:

Ring A is C 3-6 cycloalkyl or C 6-10 aryl;

R 1 is selected from H, C 1-6 alkyl, C 1-6 heteroalkyl, C 1-6 halooalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, 6- to 10-membered heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from oxo, halo, —OR 18 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 heteroalkyl, C 1 - 4 haloalkyl, —CN, and —NR 20 R 21 ;

R 2 is selected from halo, —CN, —OH, —OMe, —OEt, —NH 2 , —NHMe, —NMe 2 , Me, Et, n-Pr, i-Pr, —CF 3 , and cyclopropyl;

R 3 is selected from H, halo, —CN, —OR 18 , —SOR 15 , —SO 2 R 15 , —NR 16 R 17 , —C(O)NR 16 R 17 , —SO 2 NR 16 R 17 , —C(O)R 18 , —C(O)OR 18 , —NR 19 C(O)R 18 , —NR 19 C(O)NR 16 R 17 , NR 19 SO 2 R 15 ,—NR 19 SO 2 NR 16 R 17 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 heteroalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, and 6- to 10-membered heteroaryl;

wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from oxo, halo, —OR 18 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 heteroalkyl, C 1-4 haloalkyl, —CN, and —NR 20 R 21 ;

R 4 is selected from C 1-6 alkyl, C 2-6 heteroalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, 6- to 10-membered heteroaryl, —O(C 0-4 alkyl)C 3-6 cycloalkyl, —O(C 0-4 alkyl)(3- to 10-membered heterocycloalkyl), —O(C 0-4 alkyl)C 6-10 aryl, —O(C 0-4 alkyl)(6- to 10-membered heteroaryl), —O(C 0-4 alkyl)C(O)OR 18 , —O(C 0-4 alkyl)C(O)NR 19 SO 2 R 15 , —O(C 0-4 alkyl) SO 2 NR 19 C(O)R 18 , —O(C 3-6 cycloalkyl)C 3-6 cycloalkyl, —O(C 3-6 cycloalkyl)(3- to 10-membered heterocycloalkyl), —O(C 3-6 cycloalkyl)C 6-10 aryl, —O(C 3-6 cycloalkyl)(6- to 10-membered heteroaryl), —O(C 3-6 cycloalkyl)C(O)OR 18 , —(C 1-4 alkyl)C 3-6 cycloalkyl, —(C 1-4 alkyl)(3- to 10-membered heterocycloalkyl), —(C 1-4 alkyl)C 6-10 aryl, —(C 1-4 alkyl)(6- to 10-membered heteroaryl), and —(C 1-4 alkyl)C(O)OR 18 ; wherein each alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from C 1-4 alkyl, oxo, halo, —OR 18 , —CN, —NR 16 R 17 , —C(O)NR 16 R 17 , —SO 2 NR 16 R 17 , —C(O)R 18 , —C(O)OR 18 , —(C 1-4 alkyl)OC(O)(C 1-4 alkyl), —(C 1-4 alkyl)OC(O)OR 18 , —NR 19 C(O)R 18 , —NR 19 C(O)NR 16 R 17 , —NR 19 SO 2 R 15 , and —NR 19 SO 2 NR 16 R 17 ; and

R 4′ and R 4″ are each independently selected from H, C 1-6 -alkyl, C 2-6 heteroalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, 6- to 10-membered heteroaryl, —O(C 0-4 alkyl)C 3-6 cycloalkyl, —O(C 0-4 alkyl)(3- to 10-membered heterocycloalkyl), —O(C 0-4 alkyl)C 6-10 aryl, —O(C 0-4 alkyl)(6- to 10-membered heteroaryl), —O(C 0-4 alkyl)C(O)OR 18 , —O(C 0-4 alkyl)C(O)NR 19 SO 2 R 15 , —O(C 0-4 alkyl)SO 2 NR 19 C(O)R 18 , —O(C 3-6 cycloalkyl)C 3-6 cycloalkyl, —O(C 3-6 cycloalkyl)(3- to 10-membered heterocycloalkyl), —O(C 3-6 cycloalkyl)C 6-10 aryl, —O(C 3-6 cycloalkyl)(6- to 10-membered heteroaryl), —O(C 3-6 cycloalkyl)C(O)OR 18 , —(C 1-4 alkyl)C 3 - 6 cycloalkyl, —(C 1-4 alkyl)(3- to 10-membered heterocycloalkyl), —(C 1-4 alkyl)C 6-10 aryl, and —(C 1-4 alkyl)(6- to 10-membered heteroaryl); wherein each alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from oxo, halo, —OR 18 , —CN, —NR 16 R 17 , —C(O)NR 16 R 17 , —SO 2 NR 16 R 17 , —C(O)R 18 , —C(O)OR 18 , —(C 1-4 alkyl)OC(O)(C 1-4 alkyl), —(C 1-4 alkyl)OC(O)OR 18 , —NR 19 C(O)R 18 , —NR 19 C(O)NR 16 R 17 , NR 19 SO 2 R 15 , and —NR 19 SO 2 NR 16 R 17 ; or

R 3 is H; and R 4 , R 4 ′, and R 4″ are taken together, along with the carbon atom to which they are attached, to form —C(O)R 18 or 6- to 10-membered heteroaryl;

R 5 is selected from H, C 1-6 alkyl, C 1-6 heteroalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, and 6- to 10-membered heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from oxo, halo, —OR 18 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 heteroalkyl, C 1-4 haloalkyl, —CN, and —NR 20 R 21 ;

R 6 and R 7 are each independently selected from H, C 1-6 alkyl, C 1-6 heteroalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, 6- to 10-membered heteroaryl, —(C 1-4 alkyl)C 3-6 cycloalkyl, —(C 1-4 alkyl)(3- to 10-membered heterocycloalkyl), —(C 1-4 alkyl)C 6-10 aryl, and —(C 1-4 alkyl)(6- to 10-membered heteroaryl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from oxo, halo, —OR 18 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 heteroalkyl, C 1-4 haloalkyl, —CN, and —NR 20 R 21 ;

R 8 and R 9 are both H;

each R 10 is independently selected from halo, —CN, —OR 18 , —NR 16 R 17 ,—C(O)NR 16 R 17 ,—SO 2 NR 16 R 17 , —C(O)NR 16 R 17 , —C(O)R 18 ,—C(O)OR 18 , —NR 19 C(O)R 18 , C 1-6 alkyl, C 1-6 heteroalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more substituents selected from oxo, halo, —OR 18 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 heteroalkyl, C 1-4 halooalkyl, —CN, and —NR 20 R 21 ;

R 11 , R 12 , R 13 , and R 14 are each independently selected from H, halo, —CN, —OR 18 , —NR 16 R 17 , —C(O)NR 16 R 17 , —SO 2 NR 16 R 17 , —C(O)R 18 , —C(O)OR 18 , —NR 19 C(O)R 18 , C 1-6 alkyl, and C 1-6 haloalkyl;

each R 15 is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, and 6- to 10-membered heteroaryl;

each R 16 and R 17 is independently selected from H, C 1-4 alkyl, C 1-4 heteroalkyl, C 1-4 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, 6- to 10-membered heteroaryl; or

an R 16 and an R 17 may be taken together along with the nitrogen atom to which they are attached to form a 3- to 10-membered heterocycloalkyl;

each R 18 is independently selected from H, C 1-4 alkyl, C 1-4 heteroalkyl, C 1-4 haloalkyl, and C 3-6 cycloalkyl;

each R 19 is independently selected from H, C 1-4 alkyl, C 1-4 heteroalkyl, C 1-4 haloalkyl, and C 3-6 cycloalkyl; and

each R 20 and R 21 is independently selected from H, C 1-4 alkyl, C 1-4 heteroalkyl, C 1-4 haloalkyl, C 3-6 cyckloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, 6- to 10-membered heteroaryl; or

an R 20 and an R 21 may be taken together along with the nitrogen atom to which they are attached to form a 3- to 10-membered heterocycloalkyl; and

n is 0, 1, 2, 3, or 4.

2. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein the compound of Formula (I-A) is a compound of Formula (I-B):

3. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein Ring A is C 3-6 cycloalkyl.

4. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein Ring A is selected from the group consisting of:

5. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 11 , R 12 , R 13 , and R 14 are each independently selected from H, halo, —CN, —OR 18 , and —NR 16 R 17 .

6. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 11 is chloro, and R 12 , R 13 , and R 14 are each H.

7. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 1 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, and C 3-6 cycloalkyl.

8. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 1 is Me.

9. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 1 is H.

10. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 2 is Me.

11. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 3 is selected from H, Me, Et, —CF 3 , and cyclopropyl.

12. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 3 is H.

13. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 2 is Me and R 3 is H.

14. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein:

R 4 is selected from C 1-6 alkyl, C 2-6 heteroalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 aryl, 6- to 10-membered heteroaryl, —O(C 0-4 alkyl)C 3-6 cycloalkyl, —O(C 0-4 alkyl)(3- to 10-membered heterocycloalkyl), —O(C 0-4 alkyl)C 6-10 aryl, —O(C 0-4 alkyl)(6- to 10-membered heteroaryl), —O(C 0-4 alkyl)C(O)OR 18 , —O(C 0-4 alkyl)C(O)NR 19 SO 2 R 15 , —O(C 0 - 4 alkyl)SO 2 NR 19 C(O)R 18 , —O(C 3-6 cycloalkyl)C 3-6 cycloalkyl, —O(C 3-6 cycloalkyl)(3- to 10-membered heterocycloalkyl), —O(C 3-6 cycloalkyl)C 6-10 aryl, —O(C 3-6 cycloalkyl)(6- to 10-membered heteroaryl), —O(C 3-6 cycloalkyl)C(O)OR 18 , —(C 1-4 -alkyl)C 3-6 cycloalkyl, —(C 1-4 -alkyl)(3- to 10-membered heterocycloalkyl), —(C 1-4 -alkyl)C 6-10 aryl, —(C 1-4 -alkyl)(6- to 10-membered heteroaryl), and —(C 1-4 -alkyl)C(O)OR 18 ; wherein each alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from C 1 - 4 alkyl, oxo, halo, —OR 18 , —CN, —NR 16 R 17 , —C(O)NR 16 R 17 , —SO 2 NR 16 R 17 , —C(O)R 18 , —C(O)OR 18 , —(C 1-4 -alkyl)OC(O)(C 1-4 alkyl), —(C 1-4 -alkyl)OC(O)OR 18 , —NR 19 C(O)R 18 , —NR 19 C(O)NR 16 R 17 , —NR 19 SO 2 R 15 , and —NR 19 SO 2 NR 16 R 17 ; and

R 4 ′ and R 4 ″ are each independently selected from H, C 1-6 -alkyl, C 1-6 haloalkyl, and C 3 - 6 cycloalkyl; wherein each alkyl and cycloalkyl is independently optionally substituted with one or more substituents selected from halo, —OR 18 , —CN, and —NR 16 R 17 ; or

R 3 is H; and

R 4 , R 4 ′, and R 4 ″ are taken together, along with the carbon atom to which they are attached, to form —C(O)R 18 or 6- to 10-membered heteroaryl.

15. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein:

R 4 is selected from C 2-6 heteroalkyl, C 1-6 -haloalkyl, 6- to 10-membered heteroaryl, —O(C 0 - 4 alkyl)(3- to 10-membered heterocycloalkyl), —O(C 0-4 alkyl)C 6-10 aryl, —O(C 0-4 alkyl)(6- to 10-membered heteroaryl), —O(C 0-4 alkyl)C(O)OR 18 , —O(C 0-4 alkyl)C(O)NR 19 SO 2 R 15 , —O(C 0-4 alkyl)SO 2 NR 19 C(O)R 18 , —O(C 3-6 cycloalkyl)(6- to 10-membered heteroaryl), —O(C 3-6 cycloalkyl)C(O)OR 18 , —(C 1-4 -alkyl)(6- to 10-membered heteroaryl) and —(C 1-4 alkyl)C(O)OR 18 ; wherein each alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents selected from C 1-4 alkyl, oxo, halo, —OR 18 , —CN, —NR 16 R 17 , —C(O)NR 16 R 17 , —SO 2 NR 16 R 17 , —C(O)OR 18 , —(C 1-4 -alkyl)OC(O)(C 1-4 alkyl), —(C 1 - 4 alkyl)OC(O)OR 18 , —NR 19 C(O)R 18 , —NR 19 C(O)NR 16 R 17 , —NR 19 SO 2 R 15 , and —NR 19 SO 2 NR 16 R 17 ; and

R 4 ′ and R 4 ″ are both H; or

R 3 is H; and

R 4 , R 4 ′, and R 4 ″ are taken together, along with the carbon atom to which they are attached, to form —C(O)R 18 or 6- to 10-membered heteroaryl.

16. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein:

R 4 is selected from C 2-6 heteroalkyl, —O(C 0-4 alkyl)(6- to 10-membered heteroaryl), —O(C 0 - 4 alkyl)C(O)OR 18 , —O(C 0-4 alkyl)C(O)NR 19 SO 2 R 15 , and (C 1-4 -alkyl)C(O)OR 18 ; wherein each alkyl, heteroalkyl, and heteroaryl is independently optionally substituted with one or more substituents selected from C 1-4 -alkyl, oxo, halo, —OR 18 , —CN, —NR 16 R 17 , —C(O)NR 16 R 17 , —SO 2 NR 16 R 17 , —C(O)OR 18 , —(C 1-4 -alkyl)OC(O)(C 1-4 alkyl), —(C 1-4 -alkyl)OC(O)OR 18 , —NR 19 C(O)R 18 , —NR 19 C(O)NR 16 R 17 , —NR 19 SO 2 R 15 , and —NR 19 SO 2 NR 16 R 17 ; and

R 4 ′ and R 4 ″ are both H.

17. The compound or pharmaceutically acceptable salt of claim 16 ,

wherein R 4 is a 3- to 8-membered heteroalkyl comprising one or more O skeletal chain atom, wherein R 4 is connected through an O or a carbon in the heteroalkyl.

18. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 5 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, and C 3-6 cycloalkyl.

19. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 5 is H.

20. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 6 and R 7 are each independently selected from H and —(C 1-4 alkyl)(3- to 10-membered heterocycloalkyl); wherein each alkyl and heterocycloalkyl is independently optionally substituted with one or more substituents selected from halo, —OR 18 , —CN, and —NR 20 R 21 .

21. The compound or pharmaceutically acceptable salt of claim 10 ,

wherein one of R 6 and R 7 is H and the other is

22. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein n is 0.

23. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein R 1 is H, R 2 is Me, R 3 is H, R 5 is H, R 8 and R 9 are both H, and one of R 6 and R 7 is

H and the other is

24. The compound or pharmaceutically acceptable salt of claim 23 ,

wherein R 11 is chloro, and R 12 , R 13 , and R 14 are each H.

25. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein the compound of Formula (I) is represented by Formula (I-C), Formula (I-D), Formula (I-E), or Formula (I-F):

26. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein the compound is selected from the group consisting of:

27. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein the compound is selected from the group consisting of:

28. The compound or pharmaceutically acceptable salt of claim 1 ,

wherein the compound is

29. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt of claim 1 , and a pharmaceutically acceptable excipient.