CD73 inhibitors
Described herein are CD73 inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of cancer, infections, and neurodegenerative diseases.
1. A compound of Formula (IV), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:
wherein:
A is —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)2R 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 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 20 b;
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 (═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;
R 9 and R 10 are;
Y 3 is —CR 13 R 14 —;
Y 4 is —O—;
R 13 and R 14 are hydrogen;
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 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); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20g ;
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 Ct-Ce 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 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 (═O)R a , —NR b R c (═O)OR b , C 1 - C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 heteroalkyl, cycloalkyl, or heterocycloalkyl;
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, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
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, 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; and
R 30 , R 33 , and R 34 are each independently hydrogen, C 1 -C 20 alkyl, 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), —(CR 50 R 51 ) v OC(═O) R 40 , —(CR 50 R 51 ) v SC(═O)R 40 ), —(CR 50 R 51 ) v OC(═O)OR 40 , —(CR 50 R 51 ) v OC(═O)(CR 52 R 53 ) v C (═O)(CR 52 R 53 ) v C(═O)R 41 , or —(C 1 -C 6 alkylene)[OC(═O)R 40 ] 2 ; provided that at least one of R 30 , R 33 , or R 34 is not hydrogen;
or R 34 and R 33 are taken together with the atoms to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R 22 ;
R 40 is C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 2 alkynyl, C 1 -C 20 heteroalkyl, 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 24 ;
R 41 is a glycerol ester derivative, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 1 -C 20 heteroalkyl, 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 24 ;
R 50 and R 51 are each independently hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alky(heteroaryl), C 1 -C 6 alkyl(cycloalkyl), or C 1 -C 6 alkyl(heterocycloalkyl);
R 52 and R 53 are each independently hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, 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);
each R 22 is independently 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); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 23 ;
each R 23 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 , —C(═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, cycloalkyl, or heterocycloalkyl;
each R 24 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 , —C(═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, cycloalkyl, or heterocycloalkyl; and
v is 1, 2, 3, or 4.
2. 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 , —NR 16 C(═O)R 15 , C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl; heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20c ;
R 5 and R 6 are each hydrogen;
R 15 is C 1 -C 6 alkyl optionally substituted with one, two, or three halogen; and
R 16 is hydrogen or C 1 -C 6 alkyl optionally substituted with one, two, or three halogen; and
each R 20c is independently halogen or C 1 -C 6 alkyl.
3. 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; and
R 16 is hydrogen or C 1 -C 6 alkyl optionally substituted with one, two, or three halogen.
4. 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.
5. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 and R 7 are each independently halogen, —OH, —OR 15 , —NR 16 S(═O) 2 R 15 , —NR 16 C(═O)R 15 , C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, 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, C 1 -C 6 alkyl, or cycloalkyl; wherein each alkyl and cycloalkyl is independently optionally substituted with one, two, or three R 20d ;
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;
each R 20c independently halogen or C 1 -C 6 alkyl; and
each R 20d is independently halogen or C 1 -C 6 alkyl.
6. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 4 and R 7 are each —OH;
R 5 is halogen, C 1 -C 6 alkyl, or cycloalkyl; wherein each alkyl and cycloalkyl is independently optionally substituted with one, two, or three R 20d ;
R 6 is hydrogen; and
each R 20d is independently halogen or C 1 -C 6 alkyl.
7. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 4 and R 7 are each —OH;
R 5 is hydrogen;
R 6 is halogen, C 1 -C 6 alkyl, or cycloalkyl; wherein each alkyl and cycloalkyl is independently optionally substituted with one, two, or three R 20d ; and
each R 20d is independently halogen or C 1 -C 6 alkyl.
8. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 4 is halogen, —OH, —NR 16 S(═O) 2 R 15 ,NR 16 C(═O)R 15 , C 1 -C 6 , alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20c ;
R 7 is hydrogen;
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
each R 20c is independently halogen or C 1 -C 6 alkyl.
9. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 4 is —OH;
R 7 is hydrogen; and
R 5 and R 6 are each hydrogen.
10. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein:
R 7 is halogen, —OH, —NR 16 S(═O) 2 R 15 , —NR 16 C(═O)R 15 , C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20c ;
R 4 is hydrogen;
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
each R 20c is independently halogen or C 1 -C 6 alkyl.
11. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 7 is —OH;
R 4 is hydrogen; and
R 5 and R 6 are each hydrogen.
12. 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 alkyltheteroaryl), C 1 -C 6 alkyl(cycloalkyl), C 1 -Co alkyl(heterocycloalkyl), —S(═O)2R 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 or C 1 -C 6 alkyl; wherein each alkyl 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.
13. 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.
14. 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.
15. 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.
16. The compound of claim 15 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
each R 20a is independently halogen.
17. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
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 ;
each R 20a is independently aryl optionally substituted with one, two, or three R 21 ; and
each R 21 is independently halogen, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl.
18. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a piperidine or a pyrrolidine optionally substituted with one, two, or three R 20a ;
each R 20a is independently aryl optionally substituted with one, two, or three R 21 ; and
each R 21 is independently halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
19. The compound of claim 1 ,
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a piperidine or a pyrrolidine optionally substituted with one R 20a ; and
each R 20a is independently aryl optionally substituted with one, two, or three R 21 ; and
each R 21 is independently halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
20. 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, 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, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 20b ;
R 18 is C 1 -C 6 alkyl, cycloalkyl or C alkyl(cycloalkyl); each independently optionally substituted with one, two, or three R 20g ;
each R 20b is independently halogen or C 1 -C 6 alkyl; and
each R 20g is independently halogen or C 1 -C 6 alkyl.
21. 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 C 1 -C 6 alkyl, cycloalkyl or C 1 -C 6 alkyl(cycloalkyl); each independently optionally substituted with one, two, or three R 20g , each R 20b is independently halogen or C 1 -C 6 alkyl; and
each R 20g is independently halogen or C 1 -C 6 alkyl.
22. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 3 is halogen.
23. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
A is —O—.
24. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
A is —CH 2 —.
25. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 30 , R 33 , and R 34 are each independently hydrogen, C 1 -C 20 alkyl, 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), —(CR 50 R 51 ) v OC(═O)R 40 , or —(CR 50 R 51 ) v OC(═O)OR 40 ); provided that at least one of R 30 , R 33 , or R 34 is not hydrogen.
26. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 30 , R 33 , and R 34 are each independently hydrogen, C 1 -C 20 alkyl, aryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(cycloalkyl), —(CR 50 R 51 ) v OC(═O)R 40 , or —(CR 50 R 51 ) v OC(═O)OR 40 ;
provided that at least one of R 30 , R 33 , or R 34 is not hydrogen.
27. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 30 , R 33 , and R 34 are each independently hydrogen, C 1 -C 20 alkyl, aryl, C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(cycloalkyl); provided that at least one of R 30 , R 33 , or R 34 is not hydrogen.
28. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 30 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(cycloalkyl), —(CR 50 R 51 ) v OC(═O)R 40 , or —(CR 50 R 51 ) v OC(═O)OR 40 ; and
R 33 and R 34 are each independently hydrogen, C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(cycloalkyl), —(CR 50 R 51 ) v OC(═O)R 40 , or —(CR 50 R 51 ) v OC(═O)OR 40 .
29. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 30 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alky(aryl), or C 1 -C 6 alkyl(cycloalkyl), and
R 33 and R 34 are hydrogen or C 1 -C 6 alkyl.
30. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 30 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(cycloalkyl); and
R 33 and R 34 are hydrogen.
31. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 33 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(cycloalkyl), —(CR 50 R 51 ) v OC(═O)R 40 , or —(CR 50 R 51 ) v OC(═O)OR 40 ; and
R 30 and R 34 are each independently hydrogen, C 1 -C 20 alkyl, aryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(cycloalkyl), —(CR 50 R 51 ) v OC(═O), or —(CR 50 R 51 ) v OC(═O)OR 40 .
32. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 33 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alky(aryl), or C 1 -C 6 alkyl(cycloalkyl), and
R 30 and R 34 are hydrogen or C 1 -C 6 alkyl.
33. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 33 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(cycloalkyl); and
R 30 and R 34 are hydrogen.
34. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 34 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(cycloalkyl), —(CR 50 R 51 ) v OC(═O)R 40 , or —(CR 50 R 51 ) v OC(═O)OR 40 , and
R 33 and R 30 are each independently hydrogen, C 1 -C 20 alkyl, aryl, C 1 -C 6 alkyl(aryl), C 1 -C 6 alkyl(cycloalkyl), —(CR 50 R 51 ) v OC(═O)R 40 , or —(CR 50 R 51 ) v OC(═O)OR 40 .
35. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 34 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(cycloalkyl); and
R 33 and R 30 are hydrogen or C 1 -C 6 alkyl.
36. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein:
R 34 is C 1 -C 6 alkyl, aryl, C 1 -C 6 alkyl(aryl), or C 1 -C 6 alkyl(cycloalkyl); and
R 33 and R 30 are hydrogen.
37. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 30 , R 33 , and R 34 are each independently —(CR 50 R 51 ) v OC(═O)R 40 or —(CR 50 R 51 ) v OC(═O)OR 40 .
38. A compound or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof selected from:
wherein A is —O— or —CH 2 —.
39. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.
40. A method of inhibiting CD73 comprising contacting CD73 with a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
41. 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.