Heteroaryls and uses thereof

A compound having the following formula II-A:

• or a pharmaceutically acceptable salt thereof wherein,
• Ring A is a 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, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each occurrence of R2 is independently —R12a, -T2-R12d, or —V2-T2-R12d, or
• two adjacent R2 groups are taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms selected from nitrogen, oxygen, and sulfur;
• each occurrence of R12a is independently halogen, —CN, —NO2, —R12c, —N(R12b)2, OR12b, —SR12c, —S(O)2R12c, —C(O)R12b, —C(O)OR12b, —C(O)N(R12b)2, —S(O)2N(R12b)2, —OC(O)N(R12b)2, —N(R12e)C(O)R12b, —N(R12e)SO2R12c, —N(R12e)C(O)OR12b, —N(R12e)C(O)N(R12b)b, or —N(R12e)SO2N(R12b)2;
• each occurrence of R12b is independently hydrogen or an optionally substituted group selected from C1-6 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, or two occurrences of R12b, taken together with a nitrogen atom to which they are bound, form an optionally substituted 4-7-membered heterocyclyl ring having O—1 additional heteroatoms selected from nitrogen, oxygen, and sulfur;
• each occurrence of R12c is independently an optionally substituted group selected from C1-6 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 R12d is independently hydrogen, —N(R7b)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, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each occurrence of R12e is independently hydrogen or an optionally substituted C1-6 aliphatic group;
• each occurrence of V2 is independently —N(R12e)—, —O—, —S—, —S(O)—, —S(O)2, —C(O)—, —C(O)O—, —C(O)N(R12e)—, —S(O)2N(R12e)—, —OC(O)N(R12e)—, —N(R12e)C(O) —, —N(R12e)SO2—, —N(R12e)C(O)O—, —N(R12e)C(O)N(R12e)—, —N(R12e)SO2(R12e)—, —OC(O)—, or —C(O)N(R12e)—O—;
• and
• T2 is an optionally substituted C1-6 alkylene chain wherein the alkylene chain optionally is interrupted by —N(R13)—, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —C(O)N(R13)—, —S(O)2N(R13)—, —OC(O)N(R13)—, —N(R13)C(O)—, —N(R13)SO2—, —N(R13)C(O)O—, —N(R13)C(O)N(R13)—, —N(R13)S(O)2N(R13)—, —OC(O)—, or —C(O)N(R13)—O— or wherein T2 or a portion thereof optionally forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring, wherein R13 is hydrogen or an optionally substituted C1-4aliphatic group;
• W is —C(R7)2—, wherein one occurrence of R7 is hydrogen and the other occurrence of R7 is hydrogen, optionally substituted C1-6 aliphatic, —N(R7b)2, or F;
• and wherein each occurrence of R7b is independently hydrogen, optionally substituted C1-6 aliphatic, —C(O)R7a, or —S(O)2R7a;
• or
• wherein two occurrences of R7b, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered heterocyclic ring;
• and each occurrence of R7a is independently hydrogen or optionally substituted C1-6 aliphatic;
• G1 is N or —CR8, wherein R8 is H, —CN, halogen, —Z2-R9, C1-6 aliphatic, or 3-10-membered cycloaliphatic, wherein:
• Z2 is selected from an optionally substituted C1-3 alkylene chain, —O—, —N(R8a)—, —S—, —S(O)—, S(O)2—, —C(O)—, —CO2—, —C(O)NR8a—, —N(R8a)C(O)—, —N(R8a)CO2—, —S(O)2NR8a—, —N(R8a)S(O)2—, —OC(O)N(R8a)—, —N(R8a)C(O)NR8a—, —N(R8a)S(O)2N(R8a)—, and —OC(O)—;
• R8a is hydrogen or an optionally substituted C1-4 aliphatic, and
• R9 is hydrogen or an optionally substituted group selected from C1-6 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;
• and
• each occurrence of R14 is independently —R14a or -T1-R14d, wherein:
• each occurrence of R14a, as valency and stability permit, is independently fluorine, ═O, ═S, —CN, NO2, R14c, —N(R14b)2, OR14b, —SR14c, —C(O)R14b, —C(O)O R14b, —C(O)N(R14b)2, —S(O)2N(R14b)2, —OC(O)N(R14b)2, —N(R14e)C(O)R14b, —N(R14e)SO2R14c, —N(R14e)C(O)OR14b, —N(R14e)C(O)N(R14b)2, or —N(R14e)SO2N(R14b)2or two occurrences of R14b, taken together with a nitrogen atom to which they are bound, form an optionally substituted 4-7-membered heterocyclyl ring having O-1 additional heteroatoms selected from nitrogen, oxygen, and sulfur;
• each occurrence of R14b is independently hydrogen or an optionally substituted group selected from C1-6 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 R14c is independently an optionally substituted group selected from C1-6 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 R14d is independently hydrogen 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, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each occurrence of R14e is independently hydrogen or an optionally substituted C1-6 aliphatic group;
• and
• T1 is an optionally substituted C1-6 alkylene chain wherein the alkylene chain optionally is interrupted by —N(R14a)—, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —C(O)N(R14a)—, —S(O)2N(R14a)—, —OC(O)N(R14a)—, —N(R14a)SO2—, —N(R14a)C(O)O—, —NR14aC(O)N(R14a)—, —OC(O)—, or —C(O)N(R14a)—O— or wherein T1 or a portion thereof optionally forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring;
• n is 0-6;
• q is 0-4;
• and
• m is 1 or 2.

A compound having the formula III-A:

• or a pharmaceutically acceptable salt thereof,
• wherein G1 is N or —CR8,
• R8 is —CN;
• Ring A is a 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, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each occurrence of R2 is independently —R12a, -T2-R12d, or —V2-T2-R12d, or
• two adjacent R2 groups are taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms selected from nitrogen, oxygen, and sulfur;
• each occurrence of R12a is independently halogen, —CN, —NO2, —R12c, —N(R12b)2, —OR12b, —SR12c, —S(O)2R12c, —C(O)R12b, —C(O)OR12b, —C(O)N(R12b)2, —S(O)2N(R12b)2, —OC(O)N(R12b)2, —N(R12e)C(O)R12b, —N(R12e)SO2R12c, —N(R12e)C(O)OR12b, —N(R12e)C(O)N(R12b)2, or —N(R12e)SO2N(R12b)2;
• each occurrence of R12b is independently hydrogen or an optionally substituted group selected from C1-6 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, and sulfur, or two occurrences of R12b, taken together with a nitrogen atom to which they are bound, form an optionally substituted 4-7-membered heterocyclyl ring having O—1 additional heteroatoms selected from nitrogen, oxygen, and sulfur;
• each occurrence of R12c is independently an optionally substituted group selected from C1-6 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 R12d is independently hydrogen, —N(R7b)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, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each occurrence of R12e is independently hydrogen or an optionally substituted C1-6 aliphatic group;
• each occurrence of V2 is independently —N(R12e)—, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —C(O)N(R12e)—, —S(O)2N(R12e)—, —OC(O)N(R12e)—, —N(R12e)C(O) —, —N(R12e)SO2—, —N(R12e)C(O)O—, —N(R12e) C(O)N(R12e)—, —N(R12e)SO2N(R12e)—, —OC(O)—, or —C(O)N(R12e)—O—;
• and
• T2 is an optionally substituted C1-6 alkylene chain wherein the alkylene chain optionally is interrupted by —N(R13)—, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —C(O)N(R13)—, —S(O)2N(R13)—, —OC(O)N(R13)—, N(R13)C(O)—, —N(R13)SO2—, —N(R13)C(O)O—, —N(R13)C(O)N(R13)—, —N(R13)S(O)2N(R13)—, —OC(O)—, or —C(O)N(R13)—O— or wherein T2 or a portion thereof optionally forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring, wherein R13 is hydrogen or an optionally substituted C1-4aliphatic group;
• and
• n is 0-6.