US2022259253A1PendingUtilityA1
Cd73 inhibitors
Est. expiryNov 3, 2037(~11.3 yrs left)· nominal 20-yr term from priority
Inventors:Xiaohui DuJohn EksterowiczValeria R. FantinErica L. JacksonDaqing SunQiuping YeJared MooreTatiana Zavorotinskaya
C07F 9/65616C07H 19/056C07F 9/6561A61P 33/14A61K 31/7064A61P 31/12A61P 25/28A61K 45/06A61P 35/00C07F 9/657181A61K 31/675A61K 31/706C07H 19/23
67
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Claims
Abstract
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.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (IIa), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:
wherein;
A is —O— or —CH 2 —;
Q 1 is CW and Q 2 is N; or
Q 1 is N and Q 2 is N;
W is hydrogen, halogen, —CN, —OH, —OR a , —SH, —SR a , —S(═O)R a , —NO 2 , —NR c R d , —S(═O) 2 R a , —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 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 30 ;
Z is —NR 1 R 2 , —OR 60 , —SR 61 , or —CR 62 R 63 R 64 ;
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 15a , —S(═O) 2 NR 16a R 17a , or —C(═) 2 R 15a , wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 30a ;
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 30b ;
R 60 is hydrogen, —C(═O)R 15e , —C(═O)OR 16e , —C(═O)NR 16e R 17e , 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 30m ;
R 61 is hydrogen, —C(═O)R 15f , —C(═O)OR 16f , —C(═O)NR 16f R 17f , 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 30n ;
R 62 , R 63 , and R 64 are each independently hydrogen, halogen, —CN, —OH, —OR 15g , —SH, —SR 15g , —S(═O)R 15g , —NO 2 , —NR 16g R 17g , —S(═O) 2 R 15g , —NHS(═O) 2 R 15g , —S(═O) 2 NR 16g R 17g , —C(═O)R 15g , —OC(═O)R 15g , —C(═O)OR 16g , —OC(═O)OR 16g , —C(═O)NR 16g R 17g , —OC(═O)NR 16g R 17g , —NR 16g C(═O)NR 16g R 17g , —NR 16g C(═O)R 15g , —NR 16g C(O)OR 16g , 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 30o ;
R 3 is halogen, —CN, —OH, —OR 15b , —SR 18b , —NR 18b R 17b , 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 30c ;
R 4 and R 7 are each independently hydrogen, halogen, —OH, —OR 15c , —NR 16c S(═O) 2 R 15c , —NR 16c C(═O)R 13c , 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 30d ;
R 5 and R 6 are each independently hydrogen, halogen, —OH, —OR 15d , —NR 16c S(═O) 2 R 15d , —NR 16d C(═O)R 15d , 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 30e ;
X 1 is a bond;
Y 1 is —S(═O) 2 —;
Y 2 is —(CR 45 R 46 ) v2 —;
R 45 and R 46 are each independently hydrogen, halogen, —OH, —OR a , —NR c R d , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
v2 is 1-3;
R 15a , R 15b , R 15c , R 15d , R 15e , R 15f , R 15g are each independently 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 30g ;
R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 16g , R 17a , R 17b , R 17e , R 17f , and R 17g 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 30h ;
or R 16a and R 17a or R 16b and R 17b or R 16e and R 17c or R 16f and R 17f or R 16g and R 17g 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 18b 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), 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 30h ;
R 21 and R 22 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 23 R 24 ) w C(═O)OR 25 , —(CR 23 R 24 ) w OC(═O)R 26 , —(CR 23 R 24 ) w SC(═O)R 26 , or —(CR 23 R 24 ) w OC(═O)OR 25 ; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 30k ;
or R 21 and R 22 are taken together with the atoms to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R 30l ;
each R 23 and R 24 are independently hydrogen, halogen, —OH, —OR a , —NR c R d , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R 25 is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 heteroalkyl;
each R 26 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 heteroalkyl;
each w is independently 1-4;
each R 30 , R 30a , R 30b , R 30c , R 30d , R 30e , R 30g , R 30h , R 30i , R 30j , R 30k , R 30l , R 30m , R 30n , and R 30o are independently halogen, —CN, —OH, —OR a , —SH, —SR a , —S(═O)R a , —NO 2 , —NR c R d , —S(═O) 2 R a , —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 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 31 ;
each R 31 is independently halogen, —CN, —OH, —OR a , —SH, —SR a , —S(═O)R a , —NO 2 , —NR c R d , —S(═O) 2 R a , —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 hydroxyalkyl, C 1 -C 6 heteroalkyl, or cycloalkyl optionally substituted with one, two, or three halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R a is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R b is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl; and
R c and R d are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, 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, two, or three halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
2 . The compound of claim 1 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 and R 46 are each independently hydrogen, halogen, or C 1 -C 6 alkyl; and v2 is 1 or 2.
3 . The compound of claim 1 or 2 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 and R 46 are each hydrogen; and
v2 is 1.
4 . The compound of any one of claims 1 - 3 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
Q 1 is CW; and Q 2 is N.
5 . The compound of any one of claims 1 - 3 pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
Q 1 is N; and
Q 2 is N.
6 . The compound of any one of claims 1 - 4 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
W is hydrogen, halogen, —CN, —OH, —OR a , —NR c R d , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl, is independently optionally substituted with one, two, or three R 30 .
7 . The compound of any one of claims 1 - 4 or 6 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
W is hydrogen, halogen, —OH, —OR a , —NR c R d , C 1 -C 4 alkyl, or C 1 -C 6 haloalkyl.
8 . The compound of any one of claims 1 - 4 or 6 or 7 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
W is hydrogen.
9 . The compound of any one of claims 1 - 8 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
A is —O—.
10 . The compound of any one of claims 1 - 8 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
A is —CH 2 —.
11 . The compound of any one of claims 1 - 10 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
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 30e .
12 . The compound of any one of claims 1 - 11 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30e is independently halogen or C 1 -C 6 alkyl.
13 . The compound of any one of claims 1 - 12 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 5 and R 6 are each hydrogen.
14 . The compound of any one of claims 1 - 13 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently hydrogen, halogen, —OH, —OR 15c , —NR 16c S(═O) 2 R 15c , —NR 16c C(═O)R 15c , 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 30d .
15 . The compound of any one of claims 1 - 14 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30d is independently halogen or C 1 -C 6 alkyl.
16 . The compound of any one of claims 1 - 15 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently hydrogen, halogen, —OH, —OR 15c , —NR 16c S(═O) 2 R 15c , or —NR 16c C(═O)R 15c .
17 . The compound of any one of claims 1 - 16 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 15c and R 15d are each independently C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and R 16c and R 16d are each independently hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
18 . The compound of any one of claims 1 - 17 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 15c and R 15d are each independently C 1 -C 6 alkyl; and R 16c and R 16d are each independently hydrogen or C 1 -C 6 alkyl.
19 . The compound of any one of claims 1 - 18 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently hydrogen, halogen, or —OH.
20 . The compound of any one of claims 1 - 19 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently halogen or —OH.
21 . The compound of any one of claims 1 - 20 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each —OH.
22 . The compound of any one of claims 1 - 21 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
Z is —NR 1 R 2 .
23 . The compound of any of claims 1 - 22 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is 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), C 1 -C 6 alkyl(heterocycloalkyl), —S(═O) 2 R 15a , —S(═O) 2 NR 16a R 17a , or —C(═O) 2 R 15a ; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 30a .
24 . The compound of any of claims 1 - 23 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 15a 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; and R 15a and R 17a are each independently hydrogen, 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; and
25 . The compound of any of claims 1 - 24 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is C 1 -C 6 alkyl; and R 16a and R 17a are each independently hydrogen or C 1 -C 6 alkyl.
26 . The compound of any one of claims 1 - 25 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is C 1 -C 6 alkyl, cycloalkyl, 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 30a .
27 . The compound of any one of claims 1 - 26 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is C 1 -C 6 alkyl, cycloalkyl, or C 1 -C 6 alkyl(aryl); wherein each alkyl, cycloalkyl, and aryl is independently optionally substituted with one, two, or three R 30a .
28 . The compound of any one of claims 1 - 27 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is cycloalkyl or C 1 -C 6 alkyl(aryl); wherein each alkyl, cycloalkyl, and aryl is independently optionally substituted with one, two, or three R 30a .
29 . The compound of any one of claims 1 - 28 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30a is independently halogen, —CN, —OH, —OR a , —NR c R d , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optimally substituted with one, two, or three R 31 .
30 . The compound of any one of claims 1 - 29 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 31 is independently halogen or C 1 -C 6 alkyl.
31 . The compound of any one of claims 1 - 30 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30a is independently halogen, —CN, —OH, —OR a , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
32 . The compound of any one of claims 1 - 31 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30a is independently halogen.
33 . The compound of any one of claims 1 - 32 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 2 is hydrogen or C 1 -C 6 alkyl.
34 . The compound of any one of claims 1 - 25 , 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 31b .
35 . The compound of any one of claims 1 - 25 or 34 , 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 30b .
36 . The compound of any one of claims 1 - 25 or 34 or 35 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30b is independently aryl optionally substituted with one, two, or three R 31 ; and
each R 31 is independently halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
37 . The compound of any one of claims 1 - 25 or 34 - 36 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 30b is aryl.
38 . The compound of any one of claims 1 - 37 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 3 is halogen, —CN, —SR 18b , 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 30c .
39 . The compound of any one of claims 1 - 38 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 3 is halogen, —CN, —SR 18b , 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 30c .
40 . The compound of any one of claims 1 - 39 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 18b is cycloalkyl or C 1 -C 6 alkyl(cycloalkyl).
41 . The compound of any one of claims 1 - 40 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30c is independently halogen or C 1 -C 6 alkyl.
42 . The compound of any one of claims 1 - 38 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 3 is halogen.
43 . The compound of any one of claims 1 - 42 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 21 and R 22 are each independently hydrogen, aryl, or —(CR 23 R 24 ) w OC(═O)OR 25 .
44 . The compound of any one of claims 1 - 43 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 21 and R 22 are each hydrogen.
45 . The compound of claim 1 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, selected from:
46 . A compound of Formula (III), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:
wherein;
Q 3 and Q 4 are independently N or CW 1 ; provided that at least one of Q 3 or Q 4 is N;
W 1 is hydrogen, halogen, —CN, —OH, —OR a , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
A is —O— or —CH 2 —;
Z is —NR 1 R 2 , —OR 60 , —SR 61 , or —CR 62 R 63 R 64 ;
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 15a , —S(═O) 2 NR 16a R 17a , or —C(═O) 2 R 15a ; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 30a ;
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 30b ;
R 60 is hydrogen, —C(═O)R 15e , —C(═O)OR 16e , —C(═O)NR 16e R 17e , 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 30m ;
R 61 is hydrogen, —C(═O)R 15f , —C(═O)OR 16f , —C(═O)NR 16f R 17f , 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 30n ;
R 62 , R 63 , and R 64 are each independently hydrogen, halogen, —CN, —OH, —OR 15g , —SH, —SR 15g , —S(═O)R 15g , —NO 2 , —NR 16g R 17g , —S(═O) 2 R 15g , —NHS(═O) 2 R 15g , —S(═O) 2 NR 16g R 17g , —C(═O)R 15g , —OC(═O)R 15g , —C(═O)OR 16g , —OC(═O)OR 16g , —C(═O)NR 16g R 17g , —OC(═O)NR 16g R 17g , —NR 16g C(═O)NR 16g R 17g , —NR 16g C(═O)R 15g , —NR 16g C(═O)OR 16g , 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 30o ;
R 3 is halogen, —CN, —OH, —OR 15b , —SR 18b , —NR 16b R 17b , 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 30c ;
R 4 and R 7 are each independently hydrogen, halogen, —OH, —OR 15c , —NR 16c S(═O) 2 R 15c , —NR 16c C(═O)R 15c , 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 30d ;
R 5 and R 6 are each independently hydrogen, halogen, —OH, —OR 15d , —NR 16d S(═O) 2 R 15d , —NR 16d C(═O)R 15d , 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 30e ;
R 8 is hydrogen, halogen, —OH, —OR a , —NR c R d , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
R 9 and R 10 are each independently hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
X 1 is bond, —C(═O)—, —S(═O) 2 —, —O—, or —CR 40 R 41 —;
Y 1 is —C(═O)—, —(CR 42 R 43 ) v1 —, —S(═O) 2 —, —NR 44 —, —S—, or —O—;
Y 1 is —(CR 45 R 46 ) v2 —, —NR 47 — or —O—;
R 40 , R 41 , R 42 , R 43 , R 45 , and R 46 are each independently hydrogen, halogen, —OH, —OR a , —NR c R d , 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 30f ;
R 44 and R 47 are each independently hydrogen, —S(═O)R a , —S(═O)—R a , —S(═O) 2 NR c R d , —C(═O)R a , —C(═O)OR b , 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 30f ;
v1 and v2 are each independently 1-3;
R 15a , R 15b , R 15c , R 15d , R 15e , R 15f , R 15g are each independently 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 30g ;
R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 16g A, R 17a , R 17b , R 17e , R 17f , and R 17g 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 30h ;
or R 16a and R 17a or R 16b and R 17b or R 16e and R 17e or R 16f and R 17f or R 16g and R 17g 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 18b 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), 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 30i ;
R 21 and R 22 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 23 R 24 ) w C(═O)OR 25 , —(CR 23 R 24 ) w OC(═O)R 26 , —(CR 23 R 24 ) w SC(═O)R 26 , or —(CR 23 R 24 ) w OC(═O)OR 25 ; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 30k ;
or R 21 and R 22 are taken together with the atoms to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R 30l ;
each R 23 and R 14 are independently hydrogen, halogen, —OH, —OR a , —NR c R d , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R 25 is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 heteroalkyl;
each R 26 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 heteroalkyl;
each w is independently 1-4;
each R 30a , R 30b , R 30c , R 30d , R 30e , R 30f , R 30g , R 30h , R 30i , R 30j , R 30k , R 30l , R 30m , R 30n , R 30o , and R 30p are independently halogen, —CN, —OH, —OR a , —SH, —SR a , —S(═O)R a , —NO 2 , —NR c R d , —S(═O) 2 R a , —NHS(═O) 2 R a , —S(═O) 3 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 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 31 ;
each R 31 is independently halogen, —CN, —OH, —OR a , —SH, —SR a , —S(═O)R a , —NO 2 , —NR c R d , —S(═O) 2 R a , —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 hydroxyalkyl, C 1 -C 6 heteroalkyl, or cycloalkyl optimally substituted with one, two, or three halogen, C 1 -C 6 alkyl, or C 1 -C 4 haloalkyl;
each R a is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optimally substituted with one, two, or three halogen, —OH, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R b is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl; and
R c and R d are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, 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, two, or three halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
47 . The compound of claim 46 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
48 . The compound of claim 46 or 47 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
49 . The compound of any one of claims 46 - 48 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
50 . The compound of any one of claims 46 - 48 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
51 . The compound of any one of claims 46 - 50 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
Q 3 is N and Q 4 is CW 1 .
52 . The compound of any one of claims 46 - 50 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
Q 4 is N and Q 3 is CW 1 .
53 . The compound of any one of claims 46 - 50 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
Q 3 is N and Q 4 is N.
54 . The compound of any one of claims 46 - 53 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
W 1 is hydrogen, halogen, or C 1 -C 6 alkyl.
55 . The compound of any one of claims 46 - 54 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 8 is hydrogen or C 1 -C 6 alkyl.
56 . The compound of any one of claims 46 - 55 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 8 is hydrogen.
57 . The compound of any one of claims 46 - 56 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 9 and R 10 are each independently hydrogen or C 1 -C 6 alkyl.
58 . The compound of any one of claims 46 - 57 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 9 and R 10 are each hydrogen.
59 . The compound of any one of claims 46 - 58 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 40 and R 41 are each independently hydrogen, halogen, —OH, —OR a , —NR c R d , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
60 . The compound of any one of claims 46 - 59 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 40 and R 41 are each independently hydrogen, halogen, —OH, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
61 . The compound of any one of claims 46 - 60 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 40 and R 41 are each hydrogen.
62 . The compound of any one of claims 46 - 61 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 42 and R 43 are each independently hydrogen, halogen, —OH, —OR a , or C 1 -C 6 alkyl.
63 . The compound of any one of claims 46 - 62 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 42 and R 43 are each hydrogen.
64 . The compound of any one of claims 46 - 63 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 44 is hydrogen, —S(═O)R a , —C(═O)R a , C 1 -C 6 alkyl, C 1 -C 6 haloalkcyl, or C 1 -C 6 alkyl(aryl).
65 . The compound of any one of claims 46 - 64 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 44 is hydrogen or C 1 -C 6 alkyl.
66 . The compound of any one of claims 46 - 65 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 and R 46 are each independently hydrogen, halogen, —OH, —OR a , —NR c R d , C 1 -C 6 alkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one, two, or three R 30p .
67 . The compound of any one of claims 46 - 66 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 and R 46 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 30p .
68 . The compound of any one of claims 46 - 67 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 and R 46 are each independently hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(aryl), or cycloalkyl.
69 . The compound of any one of claims 46 - 68 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 and R 46 are each independently hydrogen or C 1 -C 6 alkyl.
70 . The compound of any one of claims 46 - 69 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 and R 46 are each hydrogen.
71 . The compound of any one of claims 46 - 67 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 is halogen, —OH, —OR a , —NR c R d , C 1 -C 6 alkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one, two, or three R 30p ; and R 46 is hydrogen or C 1 -C 6 alkyl.
72 . The compound of any one of claims 46 - 67 or 71 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 is halogen, C 1 -C 6 alkyl, or cycloalkyl; wherein each alkyl and cycloalkyl is independently optionally substituted with one, two, or three R 30p ; and
R 46 is hydrogen or C 1 -C 6 alkyl.
73 . The compound of any one of claims 46 - 67 or 71 or 72 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 is halogen, C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(aryl), or cycloalkyl; and
R 46 is hydrogen or C 1 -C 6 alkyl.
74 . The compound of any one of claims 46 - 67 or 71 - 73 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 45 is C 1 -C 6 alkyl; and
R 46 is hydrogen or C 1 -C 6 alkyl.
75 . The compound of any one of claims 46 - 74 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
A is —O—.
76 . The compound of any one of claims 46 - 74 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
A is —CH 2 —.
77 . The compound of any one of claims 46 - 76 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
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 30e .
78 . The compound of any one of claims 46 - 77 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30c is independently halogen or C 1 -C 6 alkyl.
79 . The compound of any one of claims 46 - 78 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 5 and R 6 are each hydrogen.
80 . The compound of any one of claims 46 - 79 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently hydrogen, halogen, —OH, —OR 15c , —NR 16c S(═O) 2 R 15c , —NR 16c C(═O)R 15c , 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 30d .
81 . The compound of any one of claims 46 - 80 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30d is independently halogen or C 1 -C 6 alkyl.
82 . The compound of any one of claims 46 - 80 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently hydrogen, halogen, —OH, —OR 15c , —NR 16c S(═O) 2 R 15e , or —NR 16c C(═O)R 15e .
83 . The compound of any one of claims 46 - 82 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 15c and R 15d are each independently C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and R 16c and R 16d are each independently hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
84 . The compound of any one of claims 46 - 83 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 15c and R 15d are each independently C 1 -C 6 alkyl; and R 16c and R 16d are each independently hydrogen or C 1 -C 6 alkyl.
85 . The compound of any one of claims 46 - 84 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently hydrogen, halogen, or —OH.
86 . The compound of any one of claims 46 - 85 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each independently halogen or —OH.
87 . The compound of any one of claims 46 - 86 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 4 and R 7 are each —OH.
88 . The compound of any one of claims 46 - 87 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
Z is —NR 1 R 2 .
89 . The compound of any one of claims 46 - 88 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is 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 30a .
90 . The compound of any one of claims 46 - 89 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, 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 30a .
91 . The compound of any one of claims 46 - 90 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is C 1 -C 6 alkyl, cycloalkyl, or C 1 -C 6 alkyl(aryl); wherein each alkyl, cycloalkyl, and aryl is independently optionally substituted with one, two, or three R 30a .
92 . The compound of any one of claims 46 - 91 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 1 is cycloalkyl or C 1 -C 6 alkyl(aryl); wherein each alkyl, cycloalkyl, and aryl is independently optionally substituted with one, two, or three R 30a .
93 . The compound of any one of claims 46 - 92 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30a is independently halogen, —CN, —OH, —OR a , —NR c R d , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 31 .
94 . The compound of any one of claims 46 - 93 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30a is independently halogen, —CN, —OH, —OR a , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
95 . The compound of any one of claims 46 - 94 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30a is independently halogen.
96 . The compound of any one of claims 46 - 95 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 2 is hydrogen or C 1 -C 6 alkyl.
97 . The compound of any one of claims 46 - 88 , 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 30b .
98 . The compound of any one of claims 46 - 88 or 97 , 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 an azetidine, a piperidine, a morpholine, or a pyrrolidine optionally substituted with one, two, or three R 30b .
99 . The compound of any one of claims 46 - 98 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 3 is halogen, —CN, —OR 15b , —SR 18b , —NR 16b R 17b , 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 30c .
100 . The compound of any one of claims 46 - 99 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 3 is halogen, —CN, —OR 15b , —NR 16b R 17b , C 1 -C 6 alkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one, two, or three R 30c .
101 . The compound of any one of claims 46 - 100 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 15b is C 1 -C 6 alkyl.
102 . The compound of any one of claims 46 - 101 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 16b and R 17b are independently hydrogen or is C 1 -C 6 alkyl.
103 . The compound of any one of claims 46 - 102 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 30c is independently halogen or C 1 -C 6 alkyl.
104 . The compound of any one of claims 46 - 103 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 3 is halogen.
105 . The compound of any one of claims 46 - 104 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 21 and R 22 are each independently hydrogen, aryl, or —(CR 23 R 24 ) w OC(═O)OR 25 .
106 . The compound of any one of claims 46 - 105 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 21 and R 22 are each hydrogen.
107 . The compound of any one of claims 46 - 106 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 21 and R 22 are taken together with the atoms to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R 30l .
108 . The compound of any one of claims 46 - 107 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 30l is C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optimally substituted with one, two, or three R 31 .
109 . The compound of any one of claims 46 - 108 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
R 30l is aryl optionally substituted with one, two, or three R 31 .
110 . The compound of any one of claims 46 - 109 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein;
each R 31 is independently halogen or C 1 -C 6 alkyl.
111 . The compound of claim 46 , pharmaceutically acceptable salt, solvate, or stereoisomer thereof, selected from:
112 . A pharmaceutical composition comprising a compound of any one of claims 1 - 111 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.
113 . A method of inhibiting CD73 comprising contacting CD73 with a compound of any one of claims 1 - 111 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
114 . A method of treating cancer in a subject, comprising administering to the subject a compound of any one of claims 1 - 111 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
115 . A method of treating cancer in a subject, comprising administering to the subject a pharmaceutical composition of claim 112 .
116 . The method of either of claim 114 or 115 , wherein the cancer is lung cancer, melanoma, breast cancer, ovarian cancer, colorectal cancer, gastric cancer, gallbladder cancer, prostate cancer, renal cancer, or a lymphoma.
117 . The method of any one of claims 113 - 116 , further comprising administering a second therapeutic agent.
118 . The method of claim 117 , wherein the second therapeutic agent is a chemotherapeutic agent or an immunotherapy agent.
119 . A method of treating an infection in a subject, comprising administering to the subject a compound of any one of claims 1 - 111 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
120 . A method of treating an infection in a subject, comprising administering to the subject a pharmaceutical composition of claim 112 .
121 . The method of either of claim 119 or 120 , wherein the infection is a viral infection.
122 . The method of either of claim 119 or 120 , wherein the infection is a parasitic infection.
123 . A method of treating a neurodegenerative disease in a subject, comprising administering to the subject a compound of any one of claims 1 - 111 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
124 . A method of treating a neurodegenerative disease in a subject, comprising administering to the subject a pharmaceutical composition of claim 112 .
125 . The method of either of claim 123 or 124 , wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, or autism.Join the waitlist — get patent alerts
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