Heteroaryls and uses thereof

1. A compound of formula IA or IB:

or a pharmaceutically acceptable salt thereof, wherein:

G 1 is CR 3 , wherein R 3 is H, —CN, halogen, —Z—R 5 , C 1-6 aliphatic, or 3-10-membered cycloaliphatic, wherein:

Z is selected from an optionally substituted C 1-3 alkylene chain, —O—, —N(R 3a )—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —CO 2 —, —C(O)NR 3a —, —N(R 3a )C(O)—, —N(R 3a )CO 2 —, —S(O) 2 NR 3a —, —N(R 3a )S(O) 2 —, —OC(O)N(R 3a )—, —N(R 3a )C(O)NR 3a —, —N(R 3a )S(O) 2 N(R 3a )—, and —OC(O)—;

R 3a is hydrogen or an optionally substituted C 1-4 aliphatic, and

R 5 is an optionally substituted group selected from C 1-6 aliphatic; 3-10-membered cycloaliphatic; 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 6-10-membered aryl; and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

R 1 is CY, wherein:

CY is

 wherein:

X 1 , X 2 , and X 3 , are each independently N, O, S, or CR 7 , provided that only one of X 1 , X 2 , or X 3 may be O or S,

G 2 is —N═ or —N 4′ —, wherein:

each occurrence of R 4′ is independently H, —Z 2 —R 6 , optionally substituted C 1-6 aliphatic, or optionally substituted 3-10-membered cycloaliphatic, wherein:

Z 2 is selected from an optionally substituted C 1-3 alkylene chain, —S(O)—, —S(O) 2 —, —C(O)—, —CO 2 —, —C(O)NR 4a —, and —S(O) 2 NR 4a —,

R 4a is hydrogen or an optionally substituted C 1-4 aliphatic, and

R 6 is an optionally substituted group selected from C 1-6 aliphatic, 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each occurrence of R 7 is independently hydrogen, —CN, halogen, —Z 3 —R 8 , C 1-6 aliphatic, or 3-10-membered cycloaliphatic, wherein:

Z 3 is selected from an optionally substituted C 1-3 alkylene chain, —O—, —N(R 7a )—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —CO 2 —, —C(O)NR 7a —, —N(R 7a )C(O)—, —N(R 7a )CO 2 —, —S(O) 2 NR 7a —, —N(R 7a )S(O) 2 —, —OC(O)N(R 7a )—, —N(R 7a )C(O)NR 7a —, —N(R 7a )S(O) 2 N(R 7a )—, and —OC(O)—,

R 7a is hydrogen or an optionally substituted C 1-4 aliphatic, and

R 8 is an optionally substituted group selected from C 1-6 aliphatic, 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur,

R 2 is a 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1-4 independent occurrences of R 12 , wherein R 12 is —R 12a , -T 2 -R 12d , or —V 2 -T 2 - R 12d , and:

each occurrence of R 12a is independently halogen, —CN, —NO 2 , —R 12c , —N(R 12b ) 2 , —OR 12b , —SR 12c , —S(O) 2 R 12c , —C(O)R 12b , —C(O)OR 12b , —C(O)N(R 12b ) 2 , —S(O) 2 N(R 12b ) 2 , —OC(O)N(R 12b ) 2 , —N(R 12e )C(O)R 12b , —N(R 12e )SO 2 R 12c , —N(R 12e )C(O)OR 12b ), —N(R 12e )C(O)N(R 12b ) 2 , or —N(R 12e )SO 2 N(R 12b ) 2 , or two occurrences of R 12b , taken together with a nitrogen atom to which they are bound, form an optionally substituted 4-7-membered heterocyclyl ring having 0-1 additional heteroatoms selected from nitrogen, oxygen, and sulfur;

each occurrence of R 12b is independently hydrogen or an optionally substituted group selected from C 1 -C 6 aliphatic, 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each occurrence of R 12c is independently an optionally substituted group selected from C 1 -C 6 aliphatic, 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each occurrence of R 12d is independently hydrogen or an optionally substituted from 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each occurrence of R 12e is independently hydrogen or an optionally substituted C 1-6 aliphatic group;

each occurrence of V 2 is independently —N(R 12e )—, —O—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —C(O)O—, —C(O)N(R 12e )—, —S(O) 2 N(R 12e )—, —OC(O)N(R 12e )—, —N(R 12e )C(O)—, —N(R 12e )SO 2 —, —N(R 12e )C(O)O—, —NR 12e C(O)N(R 12e )—, —N(R 12e )SO 2 N(R 12e )—, —OC(O)—, or —C(O)N(R 12e )—O—; and

T 2 is an optionally substituted C 1 -C 6 alkylene chain wherein the alkylene chain optionally is interrupted by —N(R 13 )—, —O—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —C(O)O—, —C(O)N(R 13 )—, —S(O) 2 N(R 13 )—, —OC(O)N(R 13 )—, —N(R 13 )C(O)—, —N(R 13 )SO 2 —, —N(R 13 )C(O)O—, —NR 13 C(O)N(R 13 )—, —N(R 13 )S(O) 2 N(R 13 )—, —OC(O)—, or —C(O)N(R 13 )—O— or wherein T 3 or a portion thereof optionally forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring, wherein R 13 is hydrogen or an optionally substituted C 1-4 aliphatic group;

and

HY is

wherein each HY group is optionally additionally substituted with one or more occurrences of R 10 ;

wherein R 10 is —R 10b , or —V 1 — 10c , -T 1 -R 10b , or —V 1 -T 1 -R 10b wherein:

V 1 is —NR 10a —, —NR 10a —C(O)—, —NR 10a —C(S)—, —NR 10a —C(NR 10a )—, —NR 10a C(O)OR 10a —, —NR 10a C(O)NR 10a —, —NR 10a C(O)SR 10a —, —NR 10a C(S)OR 10a —, —NR 10a C(S)NR 10a —, —NR 10a C(S)SR 10a —, —NR 10a C(NR 10a )OR 10a —, —NR 10a C(NR 10a )NR 10a —, —NR 10a S(O) 2 —, —NR 10a S(O) 2 NR 10a —, —C(O)—, —CO 2 —, —C(O)NR 10a —, —C(O)NR 10a O—, —SO 2 —, or —SO 2 NR 10a —;

each occurrence of R 10a is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

T 1 is an optionally substituted C 1 -C 6 alkylene chain wherein the alkylene chain optionally is interrupted by —N(R 10a )—, —O—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —C(O)O—, —C(O)N(R 10a )—, —S(O) 2 N(R 10a )—, —OC(O)N(R 10a )—, —N(R 10a )C(O)—, —N(R 10a )SO 2 —, —N(R 10a )C(O)O—, —NR 10a C(O)N(R 10a )—, —N(R 10a )S(O) 2 N(R 10a )—, —OC(O)—, or —C(O)N(R 10a )—O— or wherein T 1 forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring;

each occurrence of R 10b is independently hydrogen, halogen, —CN, —NO 2 , —N(R 10a ) 2 , —OR 10a , —SR 10a , —S(O) 2 R 10a , —C(O)R 10a , —C(O)OR 10a , —C(O)N(R 10a ) 2 , —S(O) 2 N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —N(R 10a )SO 2 R 10a , —N(R 10a )C(O)OR 10a , —N(R 10a )C(O)N(R 10a ) 2 , or —N(R 10a )SO 2 N(R 10a ) 2 , or an optionally substituted group selected from 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

and wherein each occurrence of R 11 is independently hydrogen, —C(O)R 11a —, —CO 2 R 11a —, —C(O)NR 11a —, C(O)NR 11a O—, —SO 2 R 11a —, —SO 2 NR 11a —, or an optionally substituted group selected from C 1-6 aliphatic, 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

wherein each occurrence of R 11a is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

2. The compound of claim 1 , wherein G 1 is CH.

3. The compound of claim 1 , wherein R 2 is an optionally substituted 6-10-membered aryl or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

4. The compound of claim 3 , wherein:

R 2 is a phenyl group substituted with 1-3 independent occurrences of halogen, C 1-3 alkyl, CN, C 1-3 haloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —NHC(O)C 1-3 alkyl, —NHC(O)NHC 1-3 alkyl, NHS(O) 2 C 1-3 alkyl, or —C(O)H.

5. The compound of claim 1 , wherein X 1 is N, G 2 is NR 4′ , and X 2 and X 3 are CR 7 .

6. The compound of claim 5 , wherein X 3 is CH.

7. The compound of claim 1 , wherein HY is selected from:

wherein each HY group is optionally additionally substituted with one or more occurrences of R 10 .

8. The compound of claim 1 , wherein HY is selected from:

wherein each HY group is optionally additionally substituted with one or more occurrences of R 10 .

9. The compound of claim 1 , wherein HY is selected from:

wherein each HY group is optionally additionally substituted with one or more occurrences of R 10 .

10. The compound of any one of claims 7 to 9 , wherein R 2 is an optionally substituted 6-10-membered aryl or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

11. The compound of any one claims 7 to 9 , wherein:

R 2 is a phenyl group substituted with 1-3 independent occurrences of halo, C 1-3 alkyl, —CN, C 1-3 haloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —NHC(O)C 1-3 alkyl, —NHC(O)NHC 1-3 alkyl, —NHS(O) 2 C 1-3 alkyl, or —C(O)H.

12. The compound of claim 1 , wherein HY is selected from:

wherein each HY group is optionally additionally substituted with one or more occurrences of R 10 .

13. The compound of claim 1 , wherein HY is selected from:

wherein each HY group is optionally additionally substituted with one or more occurrences of R 10 ; and

wherein R 2 is an optionally substituted 6-10-membered aryl or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

14. The compound of claim 13 , wherein R 2 is a phenyl group substituted with 1-3 independent occurrences of halo, C 1-3 alkyl, —CN, C 1-3 haloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —NHC(O)C 1-3 alkyl, —NHC(O)NHC 1-3 alkyl, —NHS(O) 2 C 1-3 alkyl, or —C(O)H.

15. The compound of claim 13 , wherein X1 is N and X2 and 13 are CH.

16. The compound of claim 1 , wherein R 2 is a phenyl group substituted with 1-3 independent occurrences of halo, C 1-3 alkyl, —CN, C 1-3 haloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —NHC(O)C 1-3 alkyl, —NHC(O)NHC 1-3 alkyl, —NHS(O) 2 C 1-3 alkyl, or —C(O)H.

17. The compound of claim 16 , wherein X 1 is N and X 2 and X 3 are CH.

18. The compound of claim 16 , wherein X 1 and X 2 are N, and X 3 is CH.

19. The compound of claim 1 having formula III:

wherein R 10d is hydrogen or optionally substituted C 1-4 alkyl, and R 10e is R 10 .

20. The compound of claim 19 , wherein R 10e is —V 1 —R 10c , or halogen.

21. The compound of claim 19 , wherein R 10d is hydrogen or C 1-4 alkyl, R 10e is H, hydroxy, C 1-6 alkyl, C 1-6 alkoxy optionally substituted by a group selected from hydroxy, C 1-6 alkyl-carbonylamino and amino-C 1-6 alkyl-carbonylamino, C 6-18 aryl-C 1-4 alkyl-oxy, 4- to 7-membered monocyclic aromatic heterocyclyl-C 1-4 alkyl-oxy containing, as a ring constituting atom besides carbon atom, 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom optionally substituted by C 1-6 alkyl optionally substituted by halogen and 4- to 7-membered monocyclic non-aromatic heterocyclyl-C 1-4 alkyl-oxy containing, as a ring constituting atom besides carbon atom, 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom optionally substituted by a group selected from halogen, C 1-6 alkyl, C 1-6 alkylsulfonyloxy and C 1-6 alkyl-carbonyl optionally substituted by hydroxyl, R 3 is H, and R 4′ is H.

22. The compound of claim 19 , 20 , or 21 , wherein X 1 is N and X 2 and X 3 are H.

23. The compound of claim 19 , 20 , or 21 , wherein X 1 and X 2 are N, and X 3 is H.

24. The compound of claim 19 , 20 , or 21 , wherein R 2 is an optionally substituted 6-10-membered aryl or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

25. The compound of claim 19 , 20 , or 21 , wherein:

R 2 is a phenyl group substituted with 1-3 independent occurrences of halo, C 1-3 alkyl, —CN, C 1-3 haloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —NHC(O)C 1-3 alkyl, —NHC(O)NHC 1-3 alkyl, —NHS(O) 2 C 1-3 alkyl, or —C(O)H.

26. A composition comprising a compound of claim 1 , 17 , or 19 , and a pharmaceutically acceptable carrier.

27. A compound selected from the group consisting of

1-E

2-E

3-E

4-E

5-E

6-E

7-E

1-F

2-F

3-F

4-F

5-F

6-F

or a pharmaceutically acceptable salt thereof.

28. A composition comprising a compound of claim 27 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.