| 主权项 |
1. A compound of formula I-A or I-B:or a pharmaceutically acceptable salt thereof, wherein:
G1 is N G2 is S; Ring A is an optionally substituted group selected from 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each occurrence of R2 is independently R12a, -T2-R12d, or —V2-T2-R12d, and: 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, 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 0-1 additional heteroatoms selected from nitrogen, oxygen, or sulfur;
each occurrence of R12b is independently hydrogen or an optionally substituted group selected from C1-C6 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 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, 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 R12d 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 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-C6alkylene 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; n is 0 to 4; R12 is hydrogen, halo, or an optionally substituted group selected from C1-6 aliphatic, —C(O)N(R5a)2, 3-10-membered cycloaliphatic, —N(R4b)2, —OR4a, or —SR4a; or R2 and R12 form an optionally substituted 3-10-membered cycloaliphatic; W1 is selected from —C(O)C(R4)2—, —C(R4)2C(O)—, —C(O)O—, —OC(O)—, —C(O)NR4a—, —NR4aC(O)—, —C(═NR4b)C(R4)2—, —C(R4)2C(═NR4b)—, —C(═NR4b)O—, —OC(═NR4b)—, —C(═NR4b)NR4a—, —NR4aC(═NR4b)—, —S(O)C(R4)2—, —C(R4)2S(O)—, —S(O)O—, —OS(O)—, —S(O)NR4a—, —NR4aS(O)—, —S(O)2C(R4)2—, —C(R4)2S(O)2—, —S(O)2O—, —OS(O)2—, —S(O)2NR4a—, —NR4aS(O)2—, —C(S)C(R4)2—, —C(R4)2C(S)—, —C(S)O—, —OC(S)—, —C(S)NR4a—, or —NR4aC(S)—, wherein: W2 is —(C—W3)r, or any two occurrences of W2 is independently —C(R5)═C(R5)—;
wherein each occurrence of W3 is independently —(R5)2 or ═O;r is 0 to 3;each occurrence of R4 is independently hydrogen, halo, or an optionally substituted C1-6 aliphatic or —C(O)OR4c;
each occurrence of R4a is independently hydrogen or optionally substituted C1-6 aliphatic;each occurrence of R4b is independently hydrogen, or a group selected from optionally substituted C1-6aliphatic, —OR4c, or —N(R4a)2;each occurrence of R4c is independently hydrogen or optionally substituted C1-6 aliphatic;each occurrence of R5 is independently hydrogen, halo, or an optionally substituted group selected from C1-6 aliphatic, —C(O)N(R5a)2, 3-10-membered cycloaliphatic, 6-10-membered aryl, 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, —N(R4b)2, —OR4a, or —SR4a;
each occurrence of R5a is independently hydrogen or optionally substituted C1-6 aliphatic; HY is an optionally substituted group selected from: wherein each occurrence of X4, X5, X6, and X, is independently —CR10 or N, provided no more than two occurrences of X4, X5, X6, and X7 are N; each occurrence of Q1 and O2 is independently S, O or —NR6; each occurrence of Y1, Y2, Y3, Y4, and Y5 is independently —CR10 or N;
or wherein two adjacent occurrences of X4 and X5, X6 and X7, Y1 and Q1, Y3 and Q2, or Y4 and Y5 taken together with the atom to which they are bound, form an optionally substituted fused group selected from 5-6-membered aryl, or 5-6-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;wherein R10 is —R10b, —V1—R10c, -T1-R10b, or —V-T1-R10b wherein:
V1 is —NR7—, —NR7—C(O)—, —NR7—C(S)—, —NR7—C(NR7)—, —NR7C(O)OR10a—, —NR7C(O)NR7—, —NR7C(O)SR10a—, —NR7C(S)OR10a—, —NR7C(S)NR7—, —NR7C(S)SR10a—, —NR7C(NR7)OR10a—, —NR7C(NR7)NR7—, —NR7S(O)2—, —NR7S(O)2NR7—, —C(O)—, —CO2—, —C(O)NR7—, —C(O)NR7O—, —SO2—, or —SO2NR7—; each occurrence of R10a 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; T1 is an optionally substituted C1-C6alkylene chain wherein the alkylene chain optionally is interrupted by —N(R7)—, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —C(O)N(R7)—, —S(O)2N(R7)—, —OC(O)N(R7)—, —N(R7)C(O)—, —N(R7)SO2—, —N(R10a)C(O)O—, —NR10aC(O)N(R10a)—, —N(R10a)S(O)2N(R10a)—, —OC(O)—, or —C(O)N(R7)—O— or wherein T1 forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring; each occurrence of R10b is independently hydrogen, halogen, —CN, —NO2, —N(R7)2, —OR10a, —SR10a, —S(O)2R10a, —C(O)R10a, —C(O)OR10a, —C(O)N(R7)2, —S(O)2N(R7)2, —OC(O)N(R7)2, —N(R7)C(O)R10a, —N(R7)SO2R10a, —N(R7)C(O)OR10a, —N(R7)C(O)N(R7)2, or —N(R7)SO2N(R7)2, or an optionally substituted group selected from C1-6aliphatic, 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 R10c 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or R7 and R10c 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 independently selected from nitrogen, oxygen, or sulfur; each occurrence of R7 is independently hydrogen, —C(O)R7a, —CO2R7a, —C(O)N(R7a)2, —C(O)N(R7a)—OR7a, —SO2R7a, —SO2N(R7a)2, 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
wherein each occurrence of R7a is independently hydrogen or an optionally substituted group selected from C1-6aliphatic, 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 R6 is independently hydrogen, —C(O)R6a, —CO2R6a, —C(O)N(R6b)2, —SO2R6a, —SO2N(R6b)2, 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteratoms independently selected from nitrogen, oxygen, or sulfur;
wherein each occurrence of R6a 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteratoms independently selected from nitrogen, oxygen, or sulfur; andwherein each occurrence of R6b 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, or sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteratoms independently selected from nitrogen, oxygen, or sulfur; or two occurrences of R6b taken together with the nitrogen atom to which they are bound, form an optionally substituted group selected from 3-6-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or HY is wherein 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, —S(O)2R14c, —C(O)R14b, —C(O)OR14b, —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)2), or 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 0-1 additional heteroatoms selected from nitrogen, oxygen, or sulfur;each occurrence of R14b is independently hydrogen or an optionally substituted group selected from C1-C6 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 R14C is independently an optionally substituted group selected from C1-C6aliphatic, 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 R14d 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 R14e is independently hydrogen or an optionally substituted C1-6 aliphatic group; andT1 is an optionally substituted C1-C6alkylene chain wherein the alkylene chain optionally is interrupted by —N(R14b)—, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —C(O)N(R14ab)—, —S(O)2N(R14b)—, —OC(O)N(R14b)—, —N(R14b)C(O)—, —N(R14b)SO2—, —N(R14b)C(O)O—, —NR14bC(O)N(R14b)—, —N(R14b)S(O)2N(R14b)—, —OC(O)—, or —C(O)N(R14b)—O— or wherein T1 or a portion thereof optionally forms part of an optionally substituted 3-7 membered cycloaliphatic or heterocyclyl ring; q is 0-6; m is 1 or 2; and p is 0, 1, or 2. |
