AZETIDINE AND PYRROLIDINE PARP1 INHIBITORS AND USES THEREOF

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

wherein:

R 1 is hydrogen, deuterium, halogen, —CN, —OH, —OR 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 1 -C 6 cyanoalkyl, C 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, or heterocycloalkyl;

X is N or CR 2 ;

R 2 is hydrogen, deuterium, halogen, —CN, —OH, —OR 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 1 -C 6 heteroalkyl, cycloalkyl, or heterocycloalkyl;

or R 1 and R 2 are taken together to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each optionally substituted with one or more R;

Z is N or CR 4 ;

R 4 is hydrogen, deuterium, halogen, —CN, —OH, —OR 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 1 -C 6 heteroalkyl, cycloalkyl, or heterocycloalkyl;

Y is N or CR 5 ;

R 5 is hydrogen, deuterium, halogen, —CN, —OH, —OR 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 1 -C 6 heteroalkyl, cycloalkyl, or heterocycloalkyl;

R 6 is hydrogen, deuterium, halogen, —CN, —OH, —OR 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 1 -C 6 heteroalkyl, cycloalkyl, or heterocycloalkyl;

each R 7 is independently hydrogen, deuterium, fluoro, 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, or C 1 -C 6 heteroalkyl;

or two R 7 are taken together to form a cycloalkyl or a heterocycloalkyl; each optionally substituted with one or more R;

n is 1 or 2;

each R 8 is independently deuterium, halogen, —CN, —NO 2 , —OH, —OR a , —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, or C 1 -C 6 heteroalkyl;

or two R 8 on the same carbon are taken together to form an oxo;

or two R 8 on the same carbon or adjacent carbons are taken together to form a cycloalkyl or heterocycloalkyl; each optionally substituted with one or more R;

p is 0-4;

W is absent, —C(R 9 ) 2 —, —O—, —S—, —S(═O)—, —S(═O) 2 —, —S(═O)(═NR W )—, or —NR W —;

each R 9 is independently hydrogen, deuterium, halogen, —CN, —OH, —OR a , —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, or C 1 -C 6 heteroalkyl;

or two R 9 are taken together to form a cycloalkyl or a heterocycloalkyl; each optionally substituted with one or more R;

R W is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl;

Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R 10 is independently deuterium, halogen, —CN, —NO 2 , —OH, —OR a , —OC(═O)R a , —OC(═O)OR b , —OC(═O)NR c R d , —SH, —SR a , —S(═O)R a , —S(═O) 2 R a , —S(═O) 2 NR c R d , —NR c R d , —NR b C(═O)NR c R d , —NR b C(═O)R a , —NR b C(═O)OR b , —NR b S(═O) 2 R a , —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 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted with one or more R;

q is 0-4;

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 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(heterocycloalkyl), C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted with one or more R;

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 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(heterocycloalkyl), C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted with one or more R;

each R c and R d are 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 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(heterocycloalkyl), C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted with one or more R;

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

each R is independently deuterium, halogen, —CN, —OH, -OC 1 -C 6 alkyl, —S(═O)C 1 -C 6 alkyl, —S(═O) 2 C 1 -C 6 alkyl, —S(═O) 2 NH 2 , —S(═O) 2 NHC 1 -C 6 alkyl, —S(═O) 2 N(C 1 -C 6 alkyl) 2 , —NH 2 , -NHC 1 -C 6 alkyl, -N(C 1 -C 6 alkyl) 2 , —NHC(═O)OC 1 -C 6 alkyl, —C(═O)C 1 -C 6 alkyl, —C(═O)OH, —C(═O)OC 1 -C 6 alkyl, —C(═O)NH 2 , —C(═O)N(C 1 -C 6 alkyl) 2 , —C(═O)NHC 1 -C 6 alkyl, 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, or C 1 -C 6 heteroalkyl;

or two R on the same atom form an oxo; provided that the compound of Formula (I) is not

.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 1 is halogen, C 1 -C 6 alkyl, or cycloalkyl.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 1 is cycloalkyl.

4 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 1 is ethyl.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 1 is halogen.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein X is CR 2 .

7 . The compound of claim 6 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is hydrogen.

8 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein Z is CR 4 .

9 . The compound of claim 8 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 4 is hydrogen.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein Y is N.

11 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 6 is hydrogen.

12 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein each R 7 is hydrogen.

13 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 1.

14 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 2.

15 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein each R 8 is independently C 1 -C 6 alkyl.

16 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein p is 1 or 2.

17 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein p is 1.

18 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein W is —O—.

19 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein Ring A is aryl or heteroaryl.

20 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein Ring A is 6-membered heteroaryl.

21 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein each R 10 is independently deuterium, halogen, —CN, —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 deuteroalkyl.

22 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein each R 10 is independently —C(═O)NR c R d .

23 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein q is 1 or 2.

24 . The compound of claim 1 selected from the group consisting of:

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

25 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

26 . A method of treating cancer in a subj ect in need thereof, the method comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

27 . The method of claim 26 , wherein the cancer is breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, a hematological cancer, gastrointestinal cancer, or lung cancer.