Heteroaryls and uses thereof

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Y 1 is S, O, NR 8 , wherein R 8 is hydrogen or an optionally substituted C 1-4 aliphatic;

Y 2 is C, N, wherein when Y 2 is C, R 1 is H, —CN, halogen, C 1-6 aliphatic, or 3-10-membered cycloaliphatic, and wherein Y 2 is N, R 1 is absent wherein:

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

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

R 3 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R 2 is H, halogen, or —W—R 5 , or R 5 , wherein:

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

R 2a 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

X 1 , X 2 , and X 3 are each independently N or CR 6 , wherein each occurrence of R 6 is independently hydrogen, —CN, halogen, —V—R 7 , C 1-6 aliphatic, or 3-10-membered cycloaliphatic, wherein:

V is selected from an optionally substituted C 1-3 alkylene chain, —O—, —N(R 6a )—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —CO 2 —, —C(O)NR 6a —, —N(R 6a )C(O)—, —N(R 6a )CO 2 —, —S(O) 2 NR 6a —, —N(R 6a )S(O) 2 —, —OC(O)N(R 6a )—, —N(R 6a )C(O)NR 6a —, —N(R 6a )S(O) 2 N(R 6a )—, or —OC(O)—,

R 6a is hydrogen or an optionally substituted C 1-4 aliphatic, and

R 7 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

CY is

wherein each occurrence of R 4 is independently —R 4a or -T 1 -R 4d , wherein:

each occurrence of R 4a , as valency and stability permit, is independently fluorine, ═O, ═S, —CN, —NO 2 , —R 4c , —N(R 4b ) 2 , —OR 4b , —SR 4c , —S(O) 2 R 4c , —C(O)R 4b , —C(O)OR 4b , —C(O)N(R 4b ) 2 , —S(O) 2 N(R 4b ) 2 , —OC(O)N(R 4b ) 2 , —N(R 4e )C(O)R 4b , —N(R 4e )SO 2 R 4e , —N(R 4e )C(O)OR 4b , —N(R 4e )C(O)N(R 4b ) 2 , or —N(R 4e )SO 2 N(R 4b ) 2 , or two occurrences of R 4b , 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, or sulfur;

each occurrence of R 4b 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 4c 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 4d 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 4e is independently hydrogen or an optionally substituted C 1-6 aliphatic group; and

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

n is 0-6;

m is 1 or 2;

p is 0, 1, or 2; and

represents a single or double bond.

2. The compound of claim 1 , wherein one or more substituents are selected from:

(a) Y 1 is S;

(b) Y 2 is C

(c) R 1 is CN or H;

(d) R 2 is an optionally substituted 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

(e) n is 0-2; or

(f) R 4 is —R 4a .

3. The compound of claim 2 , wherein the compound is represented by:

4. The compound of claim 1 , wherein R 2 is a 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, optionally substituted with 1-4 independent occurrences of R 9 , wherein R 9 is —R 9a , -T 2 -R 9d , or —V 2 -T 2 -R 9d , and:

each occurrence of R 9a is independently halogen, —CN, —NO 2 , —R 9c , —N(R 9b ) 2 , —OR 9b , —SR 9c , —S(O) 2 R 9c , —C(O)R 9b , —C(O)OR 9b , —C(O)N(R 9b ) 2 , —S(O) 2 N(R 9b ) 2 , —OC(O)N(R 9b ) 2 , —N(R 9e )C(O)R 9b , —N(R 9e )SO 2 R 9c , —N(R 9e )C(O)OR 9b , —N(R 9e )C(O)N(R 9b ) 2 , or —N(R 9e )SO 2 N(R 9b ) 2 , or two occurrences of R 9b , 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, or sulfur;

each occurrence of R 9b 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 9c 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 9d 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 9e is independently hydrogen or an optionally substituted C 1-6 aliphatic group;

each occurrence of V 2 is independently —N(R 9e )—, —O—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —C(O)O—, —C(O)N(R 9e )—, —S(O) 2 N(R 9e )—, —OC(O)N(R 9e )—, —N(R 9e )C(O)—, —N(R 9e )SO 2 —, —N(R 9e )C(O)O—, —NR 9e C(O)N(R 9e )—, —N(R 9e )SO 2 N(R 9e )—, —OC(O)—, or —C(O)N(R 9e )—O—; and

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

5. The compound of claim 1 , wherein Y 1 is S, Y 2 is C and the compound is represented by formula II:

wherein R 1 is CN or H.

6. The compound of claim 5 , wherein:

R 2 is an optionally substituted 3-10-membered cycloaliphatic, 4-10-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

n is 0-2; and

R 4 is —R 4a .

7. The compound of claim 6 , wherein the compound is represented by:

8. The compound of claim 7 , wherein:

R 2 is an optionally substituted 6-10-membered aryl, or a 5-10-membered heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein R 2 is optionally substituted with 1-4 independent occurrences of R 9 , wherein R 9 is —R 9a , -T 2 -R 9d , or —V 2 -T 2 -R 9d , and:

each occurrence of R 7a is independently halogen, —CN, —NO 2 , —R 7c , —N(R 7b ) 2 , —OR 7b , —SR 7c , —S(O) 2 R 9c , —C(O)R 9b , —C(O)OR 9b , —C(O)N(R 9b ) 2 , —S(O) 2 N(R 9b ) 2 , —OC(O)N(R 9b ) 2 , —N(R 9e )C(O)R 9b , —N(R 9e )SO 2 R 9c , —N(R 9e )C(O)OR 9b , —N(R 9e )C(O)N(R 9b ) 2 , or —N(R 9e )SO 2 N(R 9b ) 2 ;

each occurrence of R 9b 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of R 9b , 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, or sulfur;

each occurrence of R 9c 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 9d 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each occurrence of R 9e is independently hydrogen or an optionally substituted C 1-6 aliphatic group;

each occurrence of V 2 is independently —N(R 7e )—, —O—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —C(O)O—, —C(O)N(R 9e )—, —S(O) 2 N(R 9e )—, —OC(O)N(R 9e )—, —N(R 9e )C(O)—, —N(R 9e )SO 2 —, —N(R 9e )C(O)O—, —NR 9e C(O)N(R 9e )—, —N(R 9e )SO 2 N(R 9e )—, —OC(O)—, or —C(O)N(R 9e )—O—; and

T 2 is an optionally substituted C 1 -C 6 alkylene chain wherein the alkylene chain optionally is interrupted by —N(R 9a )—, —O—, —S—, —S(O)—, —S(O) 2 —, —C(O)—, —C(O)O—, —C(O)N(R 9a )—, —S(O) 2 N(R 9a )—, —OC(O)N(R 9a )—, —N(R 9a )C(O)—, —N(R 9a )SO 2 —, —N(R 9a )C(O)O—, —NR 9a C(O)N(R 9a )—, —N(R 9a )S(O) 2 N(R 9a )—, —OC(O)—, or —C(O)N(R 9a )—O— or wherein T 2 or a portion thereof optionally forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring; and

n is 0-2.

9. The compound of claim 8 , wherein:

R 2 is a phenyl group substituted with 1-3 independent occurrences of halogen, —CN, —NO 2 , —R 9c , —N(R 9b ) 2 , —OR 9b , —SR 9c , —S(O) 2 R 9c , —C(O)R 9b , —C(O)OR 9b , —C(O)N(R 9b ) 2 , —S(O) 2 N(R 9b ) 2 , —OC(O)N(R 9b ) 2 , —N(R 9e )C(O)R 9b , —N(R 9e )SO 2 R 9c , —N(R 9e )C(O)OR 9b , —N(R 9e )C(O)N(R 9b ) 2 , or —N(R 9e )SO 2 N(R 9b ) 2 ;

R 3 is hydrogen, C 1-4 alkyl, or C 1-4 fluoroalkyl; and

n is 0.

10. The compound of claim 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 —COH.

11. The compound of claim 1 , wherein the compound is selected from:

12. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.