CD73 inhibitors

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

wherein:

A —O— or —CH 2 —;

R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(heteroaryl), C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(heterocycloalkyl), —S(═O) 2 R 15 , —S(═O) 2 NR 16 R 17 , or —C(═O) 2 R 15 ; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20a ;

or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R 20a ;

R 3 is halogen, —CN, OR 15 , SR 18 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(heteroaryl), C 1 -C 6 alkyl(cycloalkyl), or C 1 -C 6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20b ;

R 4 and R 7 are each independently hydrogen, halogen, —OH, —OR 15 , —NR 16 S(═O) 2 R 15 , —NR 16 C(═O)R 15 , C 1 -C 6 alkyl, 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, two, or three R 20c ;

R 5 and R 6 are each independently hydrogen, halogen, —OH, —OR 15 , —NR 16 S(═O) 2 R 15 , —NR 16 C(═O)R 15 , C 1 -C 6 alkyl, 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, two, or three R 20d ;

R 8 is hydrogen, halogen, or C 1 -C 6 alkyl optionally substituted with one, two, or three halogen;

R 9 and R 10 are each independently hydrogen, halogen, or C 1 -C 6 alkyl optionally substituted with one, two, or three halogen;

X is —O— or —CR 11 R 12 —;

R 11 and R 12 are each independently hydrogen, halogen, or C 1 -C 6 alkyl optionally substituted with one, two, or three halogen;

Y 1 , Y 2 , and Y 3 are independently —O—, —S—, or —CR 13 —R 14 —;

R 13 and R 14 are each independently hydrogen, halogen, —OH, —OR 15 , —NR 16 R 17 , C 1 -C 6 alkyl optionally substituted with one, two, or three halogen;

R 15 is C 1 -C 6 alkyl, 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, two, or three R 20e ;

R 16 and R 17 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl, is independently optionally substituted with one, two, or three R 20f ;

or R 16 and R 17 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

R 18 is C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(heteroaryl), C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20g ;

n, m, and p, are each independently 0 or 1;

each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently halogen, —CN, —OH, —OR a , —SH, —SR a ,—S(═O)R a , —NO 2 , —NR b R c , —S(═O) 2 R a , —NHS(═O) 2 R a , —S(═O) 2 NR b R c , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR b R c , —OC(═O)NR b R c , —NR b C(═O)NR b R c , —NR b C(═O)R a , —NR b C(═O)OR b , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(heteroaryl), C 1 -C 6 alkyl(cycloalkyl), or C 1 -C 6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 21 ;

each R 21 is independently halogen, —CN, —OH, —OR a , —SH, —SR a , —S(═O)R a , —NO 2 , —NR b R c , —S(═O) 2 R a , —NHS(═O) 2 R a , —S(═O) 2 NR b R c , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR b R c , —OC(═O)NR b R c , —NR b C(═O)NR b R c , —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 hydroxyalkyl, C 1 -C 6 heteroalkyl, or cycloalkyl;

each R a is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and

R b and R c are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

or R b and R c are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

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

R 8 is hydrogen.

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

R 9 and R 10 are each hydrogen.

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

X is —O—.

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

n is 1;

m and p are each 0;

Y 3 is —O— or —CR 13 R 14 —; and

R 13 and R 14 are each independently hydrogen, halogen, or C 1 -C 6 alkyl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the compound of Formula (A) is of Formula (Ab):

7. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

R 4 and R 7 are each independently halogen, —OH, —OR 15 , —NR 16 S(═O) 2 R 15 , or —NR 16 C(═O)R 15 ;

R 5 and R 6 are each hydrogen;

R 15 is C 1 -C 6 alkyl optionally substituted with one, two, or three halogen;

R 16 is hydrogen or C 1 -C 6 alkyl optionally substituted with one, two, or three halogen; and

R 15 is C 1 -C 6 alkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

R 4 and R 7 are each —OH; and

R 5 and R 6 are each hydrogen.

9. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the compound of Formula (A) is of Formula (Ac):

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

R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(heteroaryl), C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(heterocycloalkyl), —S(═O) 2 R 15 , —S(═O) 2 NR 16 R 17 or —C(═O) 2 R 15 ; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20a ;

R 2 is hydrogen;

R 15 is C 1 -C 6 alkyl, aryl, or C 1 -C 6 alkyl(aryl); wherein each alkyl and aryl is optionally substituted with one, two, or three halogen;

R 16 and R 17 are each independently hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 alkyl(aryl); wherein each alkyl and aryl is optionally substituted with one, two, or three halogen; and

each R 20a is independently halogen, —CN, —OH, —OC 1 —C 6 alkyl, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

11. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

R 1 is C 1 -C 6 alkyl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(heteroaryl), C 1 -C 6 alkyl(cycloalkyl), or C 1 -C 6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20a ;

R 2 is hydrogen; and

each R 20a is independently halogen, —CN, —OH, —OC 1 —C 6 alkyl, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

12. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

R 1 is C 1 -C 6 alkyl or C 1 -C 6 alkyl(aryl); wherein each alkyl and aryl is independently optionally substituted with one, two, or three R 20a ;

R 2 is hydrogen; and

each R 20a is independently halogen, —CN, —OH, —OC 1 —C 6 alkyl, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

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

R 1 is C 1 -C 6 alkyl or C 1 -C 6 alkyl(aryl); wherein aryl is optionally substituted with one R 20a ;

R 2 is hydrogen; and

each R 20a is independently halogen, —CN, —OH, —OC 1 —C 6 alkyl, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

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

R 3 is halogen, —CN, SR 18 , C 1 -C 6 alkyl, or C 1 -C 6 alkyl(cycloalkyl); wherein each alkyl, and cycloalkyl is independently optionally substituted with one, two, or three R 20b ;

R 18 is cycloalkyl or C 1 -C 6 alkyl(cycloalkyl); and

each R 20b is independently halogen or C 1 -C 6 alkyl.

15. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

R 3 is halogen.

16. The compound of claim 1 , wherein the compound of Formula (A) or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof is selected from:

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

18. A method of treating cancer in a subject, comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

19. A method of treating an infection in a subject, comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

20. A method of treating a neurodegenerative disease in a subject, comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.