IP Library › Patent Application 18002557

Patent Application

App. No. 18/002,557

TREX1 INHIBITORS AND USES THEREOF

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App. No.: 18/002,557

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Abstract

Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds for inhibiting three prime repair exonuclease 1 (“TREX1”).

Claims (317)

1 . A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof:

wherein:

Ring A is

Ring B is phenyl or a 6-membered heteroaryl;

R 1 is hydrogen, deuterium, halogen, —CN, —OR 11 , —SR 11 , —S(═O)R 10 , —S(═O) 2 R 10 , —NO 2 , —NR 12 R 13 , —NHS(═O) 2 R 10 , —S(═O) 2 NR 12 R 13 , —C(═O)R 10 , —OC(═O)R 10 , —C(═O)OR 11 , —OC(═O)OR 11 , —C(═O)NR 12 R 13 , —OC(═O)NR 12 R 13 , —NR 11 C(═O)NR 12 R 13 , —NR 11 C(═O)R 10 , —NR 11 C(═O)OR 11 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 1a ;

each R 2 is independently hydrogen, deuterium, halogen, —CN, —OR b , —SR b , —S(═O)R a , —S(═O) 2 R a , —NO 2 , —NR c R d , —NHS(═O) 2 R a , —S(═O) 2 NR c R d , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR c R d , —OC(═O)NR c R d , —NR b C(═O)NR c R d , —NR b C(═O)R a , —NR b C(═O)OR b , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 2a ;

n is 1-3;

Y 1 is O, S, or NR Y1 ;

Y 2 is N or CR Y2 ;

provided that when Y 2 is CR Y2 , Y 1 is not O;

R Y1 is hydrogen, —S(═O)R a , —S(═O) 2 R a , —S(═O) 2 NR W R d , —C(═O)R a , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R Y1a .

R Y2 is hydrogen, deuterium, halogen, —CN, —OR b , —NO 2 , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R Y2a ;

R 3 is hydrogen, deuterium, halogen, —CN, —OR b , —NO 2 , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 3a ;

R 4 is hydrogen, deuterium, halogen, —CN, —OR b , —NO 2 , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 4a ;

R 6 is —C(═O)R a , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 6a ;

or R 4 and R 6 are taken together to form a heterocycloalkyl optionally substituted with deuterium, halogen, —CN, —OR b , —NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R 1a is independently deuterium, halogen, —CN, —OR 11 , —SR 11 , —S(═O)R 10 , —S(═O) 2 R 10 , —NO 2 , —NR 12 R 13 , —NHS(═O) 2 R 10 , —S(═O) 2 NR 12 R 13 , —C(═O)R 10 , —OC(═O)R 10 , —C(═O)OR 11 , —OC(═O)OR 11 , —C(═O)NR 12 R 13 , —OC(═O)NR 12 R 13 , —NR 11 C(═O)NR 12 R 13 , —NR 11 C(═O)R 10 , —NR 11 C(═O)OR 11 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 1b ;

or two R 1a on the same carbon are taken together to form an oxo;

each R 10 is independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 10a ;

each R 11 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 11a ;

each R 12 and R 13 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 12a ;

or R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R 13a ;

each R Y1a , R Y2a , R 2a , R 3a , R 4a , R 6a , R 10a , R 11a , R 12a , R 13a , and R 1b is independently deuterium, halogen, —CN, —OR b , —SR b , —S(═O)R a , —S(═O) 2 R a , —NO 2 , —NR c R d , —NHS(═O) 2 R a , —S(═O) 2 NR c R d , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR c R d , —OC(═O)NR c R d , —NR b C(═O)NR c R d , —NR b C(═O)R a , —NR b C(═O)OR b , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

or two R Y1a , two R Y2a , two R 2a , two R 3a , two R 4a , two R 5a , two R 6a , two R 10a , two R 11a , two R 12a , two R 13a , and two R 1b on the same carbon are taken together to form an oxo, a cycloalkyl, or a heterocycloalkyl;

wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

each R b is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl; and

each R c and R d is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

or R c and R d are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

provided that the compound of Formula (I) is not

2 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (I) is of Formula (Ia):

3 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (I) is of Formula (Ib):

4 . The compound of any one of claims 1 - 3 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

5 . The compound of any one of claims 1 - 4 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

6 . The compound of any one of claims 1 - 4 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

7 . The compound of any one of claims 1 - 4 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

8 . The compound of any one of claims 1 - 4 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

9 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

Y 1 is S and Y 2 is N.

10 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

Y 1 is O and Y 2 is N.

11 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

Y 1 is NR Y1 and Y 2 is N.

12 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

Y 1 is NR Y1 and Y 2 is CR Y2 .

13 . The compound of any one of claims 1 - 8 or 12 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is hydrogen, C 1 -C 6 alkyl, or heterocycloalkyl.

14 . The compound of any one of claims 1 - 8 or 12 or 13 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is hydrogen.

15 . The compound of any one of claims 1 - 8 or 12 or 13 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is heterocycloalkyl.

16 . The compound of any one of claims 1 - 8 or 12 - 15 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y2 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R Y2a .

17 . The compound of any one of claims 1 - 8 or 12 - 16 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y2 is hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

18 . The compound of any one of claims 1 - 8 or 12 - 17 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y2 is hydrogen.

19 . The compound of any one of claims 1 - 18 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

20 . The compound of any one of claims 1 - 19 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen or halogen.

21 . The compound of any one of claims 1 - 20 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen.

22 . The compound of any one of claims 1 - 21 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

23 . The compound of any one of claims 1 - 22 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen or halogen.

24 . The compound of any one of claims 1 - 23 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen.

25 . The compound of any one of claims 1 - 24 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 6 is C 1 -C 6 alkyl.

26 . The compound of any one of claims 1 - 25 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 6 is methyl.

27 . The compound of any one of claims 1 - 26 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

28 . The compound of any one of claims 1 - 27 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

29 . The compound of any one of claims 1 - 28 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

30 . The compound of any one of claims 1 - 29 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen or halogen.

31 . The compound of any one of claims 1 - 30 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is hydrogen.

32 . The compound of any one of claims 1 - 31 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

n is 1 or 2.

33 . The compound of any one of claims 1 - 32 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

n is 1.

34 . The compound of any one of claims 1 - 33 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is hydrogen, deuterium, halogen, —CN, —OR 11 , —NR 12 R 13 , —C(═O)R 10 , —C(═O)OR 11 , —C(═O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 1a .

35 . The compound of any one of claims 1 - 34 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is hydrogen, deuterium, halogen, —CN, —OR 11 , —NR 12 R 13 , —C(═O)R 10 , —C(═O)OR 11 , —C(═O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

36 . The compound of any one of claims 1 - 35 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

37 . The compound of any one of claims 1 - 36 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is hydrogen or halogen.

38 . The compound of any one of claims 1 - 37 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is hydrogen.

39 . The compound of any one of claims 1 - 34 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 1a .

40 . The compound of any one of claims 1 - 34 or 39 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is heterocycloalkyl optionally substituted with one or more R 1a .

41 . The compound of any one of claims 1 - 34 or 39 or 40 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is heterocycloalkyl optionally substituted with one or more R 1a ; wherein the heterocycloalkyl is piperidinyl or piperazinyl.

42 . The compound of any one of claims 1 - 34 or 39 - 41 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is piperidinyl optionally substituted with one or more R 1a .

43 . The compound of any one of claims 1 - 34 or 39 - 41 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 1 is piperazinyl optionally substituted with one or more R 1a .

44 . The compound of any one of claims 1 - 34 or 39 - 43 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 1a is independently deuterium, halogen, —CN, —OR 11 , —S(═O) 2 R 10 , —NR 12 R 13 , —NHS(═O) 2 R 10 , —S(═O) 2 NR 12 R 13 , —C(═O)R 10 , —C(═O)OR 11 , —C(═O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 1b ; or two R 1a on the same carbon are taken together to form an oxo.

45 . The compound of any one of claims 1 - 34 or 39 - 44 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 1a is independently halogen, —CN, —OR 11 , —S(═O) 2 R 10 , —NR 12 R 13 , —NHS(═O) 2 R 10 , —S(═O) 2 NR 12 R 13 , —C(═O)R 10 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted with one or more R 1b ; or two R 1a on the same carbon are taken together to form an oxo.

46 . The compound of any one of claims 1 - 34 or 39 - 45 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 1a is independently —C(═O)R 10 .

47 . The compound of any one of claims 1 - 34 or 39 - 46 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

wherein each alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 10a .

48 . The compound of any one of claims 1 - 34 or 39 - 47 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 aminoalkyl, aryl, or heteroaryl;

wherein each alkyl, alkenyl, aryl, and heteroaryl is independently optionally substituted with one or more R 10a .

49 . The compound of any one of claims 1 - 33 or 38 - 47 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10 is independently aryl optionally substituted with one or more R 10a .

50 . The compound of any one of claims 1 - 33 or 38 - 48 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10a is independently deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

51 . The compound of any one of claims 1 - 34 or 39 - 50 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10a is independently halogen, —OR b , —C(═O)OR b , or C 1 -C 6 alkyl.

52 . A compound of Formula (II) or (III), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof:

wherein:

Ring A is

Ring C is cycloalkyl or heterocycloalkyl;

each R C is independently deuterium, halogen, —CN, —OR 11 , —SR 11 , —S(═O)R 10 , —S(═O) 2 R 10 , —NO 2 , —NR 12 R 13 , —NHS(═O) 2 R 10 , —S(═O) 2 NR 12 R 13 , —C(═O)R 10 , —OC(═O)R 10 , —C(═O)OR 11 , —OC(═O)OR 11 , —C(═O)NR 12 R 13 , —OC(═O)NR 12 R 13 , —NR 11 C(═O)NR 12 R 13 , —NR 11 C(═O)R 10 , —NR 11 C(═O)OR 11 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R Ca ;

or two R C on the same carbon are taken together to form an oxo;

m is 1-3,

n is 1-3;

R Y1 is hydrogen, —S(═O)R a , —S(═O) 2 R a , —S(═O) 2 NR c R d , —C(═O)R a , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R Y1a ;

R 5 is hydrogen, deuterium, halogen, —CN, —OR b , —NO 2 , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more R 5a ;

or R 4 and R 5 are taken together to form a heterocycloalkyl optionally substituted with deuterium, halogen, —CN, —OR b , —NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

or R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R 13a .

each R Y1a , R 2a , R 3a , R 4a , R 5a , R 6a , R 10a , R 11a , R 12a , R 13a , and R Ca is independently deuterium, halogen, —CN, —OR b , —SR b , —S(═O)R a , —S(═O) 2 R a , —NO 2 , —NR c R d , —NHS(═O) 2 R a , —S(═O) 2 NR c R d , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR c R d , —OC(═O)NR c R d , —NR b C(═O)NR c R d , —NR b C(═O)R a , —NR b C(═O)OR b , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

or two R Y1a , two R 2a , two R 3a , two R 4a , two R 5a , two R 6a , two R 10a , two R 11a , two R 12a , two R 13a , and two R Ca on the same carbon are taken together to form an oxo, a cycloalkyl, or heterocycloalkyl;

each R a is independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

53 . The compound of claim 52 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (II) is of Formula (IIa):

54 . The compound of claim 52 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (II) is of Formula (IIb):

55 . The compound of claim 52 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (II) is of Formula (IIc):

56 . The compound of claim 51 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (II) is of Formula (IId):

57 . The compound of claim 51 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (III) is of Formula (IIIa):

58 . The compound of claim 51 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (III) is of Formula (IIIb):

59 . The compound of claim 51 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (III) is of Formula (IIIc):

60 . The compound of claim 51 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (III) is of Formula (IIId):

61 . The compound of any one of claims 52 - 60 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is hydrogen, C 1 -C 6 alkyl, or heterocycloalkyl.

62 . The compound of any one of claims 52 - 61 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is hydrogen.

63 . The compound of any one of claims 52 - 62 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is heterocycloalkyl.

64 . The compound of any one of claims 52 - 63 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R, —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

65 . The compound of any one of claims 52 - 64 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen or halogen.

66 . The compound of any one of claims 52 - 65 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen.

67 . The compound of any one of claims 52 - 66 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

68 . The compound of any one of claims 52 - 67 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen or halogen.

69 . The compound of any one of claims 52 - 68 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen.

70 . The compound of any one of claims 52 - 69 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 5 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

71 . The compound of any one of claims 52 - 70 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 5 is hydrogen or halogen.

72 . The compound of any one of claims 52 - 71 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 5 is hydrogen.

73 . The compound of any one of claims 52 - 72 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 6 is C 1 -C 6 alkyl.

74 . The compound of any one of claims 52 - 73 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 6 is methyl.

75 . The compound of any one of claims 52 - 74 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

76 . The compound of any one of claims 52 - 75 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

77 . The compound of any one of claims 52 - 76 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

78 . The compound of any one of claims 52 - 77 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen or halogen.

79 . The compound of any one of claims 52 - 78 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is hydrogen.

80 . The compound of any one of claims 52 - 79 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

n is 1 or 2.

81 . The compound of any one of claims 52 - 79 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

n is 1.

82 . The compound of any one of claims 52 - 81 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

Ring C is heterocycloalkyl.

83 . The compound of any one of claims 52 - 81 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

Ring C is cycloalkyl.

84 . The compound of any one of claims 52 - 83 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R C is independently deuterium, halogen, —CN, —OR 11 , —S(═O) 2 R 10 , —NR 12 R 13 , —NHS(═O) 2 R 10 , —S(═O) 2 NR 12 R 13 , —C(═O)R 10 , —C(═O)OR 11 , —C(═O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R Ca ; or two R C on the same carbon are taken together to form an oxo.

85 . The compound of any one of claims 52 - 83 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R C is independently halogen, —CN, —OR 11 , —S(═O) 2 R 10 , —NR 12 R 13 , —NHS(═O) 2 R 10 , —S(═O) 2 NR 12 R 13 , —C(═O)R 10 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted with one or more R Ca ; or two R C on the same carbon are taken together to form an oxo.

86 . The compound of any one of claims 52 - 85 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R C is independently —C(═O)R 10 .

87 . The compound of any one of claims 52 - 86 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 10a .

88 . The compound of any one of claims 52 - 87 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 aminoalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, aryl, and heteroaryl is independently optionally substituted with one or more R 10a .

89 . The compound of any one of claims 52 - 88 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10 is independently aryl optionally substituted with one or more R 10a .

90 . The compound of any one of claims 52 - 89 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10a is independently deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

91 . The compound of any one of claims 52 - 90 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 10a is independently halogen, —OR b , —C(═O)OR b , or C 1 -C 6 alkyl.

92 . A compound of Formula (IV) and (V), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof:

wherein

Ring A is

n is 1-3;

or two R Y1a , two R 2a , two R 3a , two R 4a , two R 5a , and two R 6a on the same carbon are taken together to form an oxo;

93 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (IV) is of Formula (IVa):

94 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (IV) is of Formula (IVb):

95 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (IV) is of Formula (IVc):

96 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (IV) is of Formula (IVd):

97 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (V) is of Formula (Va):

98 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (V) is of Formula (Vb):

99 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (V) is of Formula (Vc):

100 . The compound of claim 92 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein the compound of Formula (V) is of Formula (Vd):

101 . The compound of any one of claims 92 - 100 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is hydrogen, C 1 -C 6 alkyl, or heterocycloalkyl.

102 . The compound of any one of claims 92 - 101 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is hydrogen.

103 . The compound of any one of claims 92 - 102 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is heterocycloalkyl.

104 . The compound of any one of claims 92 - 103 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

105 . The compound of any one of claims 92 - 104 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen or halogen.

106 . The compound of any one of claims 92 - 105 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 3 is hydrogen.

107 . The compound of any one of claims 92 - 106 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

108 . The compound of any one of claims 92 - 107 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen or halogen.

109 . The compound of any one of claims 92 - 108 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 4 is hydrogen.

110 . The compound of any one of claims 92 - 109 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 5 is hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

111 . The compound of any one of claims 92 - 110 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 5 is hydrogen or halogen.

112 . The compound of any one of claims 92 - 111 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 5 is hydrogen.

113 . The compound of any one of claims 92 - 112 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 6 is C 1 -C 6 alkyl.

114 . The compound of any one of claims 92 - 113 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R 6 is methyl.

115 . The compound of any one of claims 92 - 114 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

116 . The compound of any one of claims 92 - 115 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen, deuterium, halogen, —CN, —OR b , —NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

117 . The compound of any one of claims 92 - 116 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

118 . The compound of any one of claims 92 - 117 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is independently hydrogen or halogen.

119 . The compound of any one of claims 92 - 118 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

each R 2 is hydrogen.

120 . The compound of any one of claims 92 - 119 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

n is 1 or 2.

121 . The compound of any one of claims 92 - 120 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

n is 1.

122 . The compound of any one of claims 1 - 121 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is cycloalkyl or heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is optionally substituted with one or more R Y1a .

123 . The compound of any one of claims 1 - 122 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is cycloalkyl optionally substituted with one or more R Y1a .

124 . The compound of any one of claims 1 - 122 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is a bicyclic cycloalkyl optionally substituted with one or more R Y1a .

125 . The compound of any one of claims 1 - 122 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is heterocycloalkyl optionally substituted with one or more R Y1a .

126 . The compound of any one of claims 1 - 122 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is

127 . The compound of any one of claims 1 - 122 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, wherein:

R Y1 is

128 . A compound selected from the group consisting of a compound found in table 1, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof.

129 . A pharmaceutical composition comprising the compound of any one of claims 1 - 128 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

130 . A method of treating cancer in a subject in need thereof, the method comprising administering the compound of any one of claims 1 - 128 , or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof.

131 . The method of claim 130 , wherein the cancer is characterized by a deficiency in one or more DNA repair pathways.

132 . The method of claim 130 , wherein the DNA repair deficiency is a deficiency in the base excision repair (“BER”) pathway, the Fanconi anaemia-mediated repair (“FA”) pathway, the homologous recombination (“HR”) pathway, the nucleotide excision repair (“NER”) pathway, the non-homologous end joining (“NHEJ”) pathway, the mismatch repair (“MMR”) pathway, the RecQ-mediated repair (“RecQ”) pathway, or the double-stranded breaks (“DSB”) pathway.

133 . The method of claim 131 or claim 132 , wherein the DNA repair deficiency is a deficiency in the homologous recombination (“HR”) pathway.

134 . The method of any one of claims 131 - 133 , wherein the DNA repair deficiency is a BRCA1 mutation.

135 . The method of any one of claims 131 - 134 , further comprising administering a DNA repair inhibitor.

136 . The method of claim 135 , wherein the DNA repair inhibitor is a poly ADP ribose polymerase (“PARP”) inhibitor.

137 . The method of any one of claims 131 - 134 , further comprising administering an alkylating agent.

138 . The method of claim 137 , wherein the alkylating agent is cyclophosphamide, chlormethine, uramustine, melphalan, chlorambucil, ifosfamide, bendamustine, carmustine, lomustine, nimustine, fotemustine, streptozocin, or busulfan.

139 . The method of any one of claims 131 - 134 , further comprising administering a DNA damaging agent.

140 . The method of claim 139 , wherein the DNA damaging agent is camptothecin, etoposide, oxaliplatin, cisplatin, or doxorubicin.

141 . The method of any one of claims 131 - 134 , wherein the compound is administered in conjunction with high-dose radiotherapy.

142 . The method of claim 141 , wherein the high-dose radiotherapy is administered as a single dose and/or hypofractionated.

143 . The method of any one of claims 131 - 140 , wherein the compound is administered in conjunction with Stereotactic Body Radiation Therapy (SBRT).

Assignments (5)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 20, 2022

From: DUBENSKY, THOMAS WALTER, JR.; CLARK, RYAN C.

To: TEMPEST THERAPEUTICS, INC.

Reel/Frame 062164/0747 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 20, 2022

From: ERNST, JUSTIN; PACKARD, GARRICK K.; BUSCH, BRETT; NAGAMIZO, JOE FRED

To: INCEPTION THERAPEUTICS, INC.

Reel/Frame 062164/0793 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 20, 2022

From: KALITA, BISWAJIT; DURAISWAMY, ATHISAYAMANI JEYARAJ

To: JUBILANT BIOSYS LIMITED