| 主权项 |
1. A compound of formula IA-a or IB-a:or a pharmaceutically acceptable salt thereof, wherein:
Z is S or Se; R1 is CY, —C(O)N(R3)2, —C(O)OR3, —C(O)(NH)OH, —C(═NH)NHOH, —C(O)NR3N(R3)2, —C(═N—NH2)NH2, or —C(═N)N(R3)2, wherein CY iswherein:
G2 is —N═, ═N—, or —N(R3′)—, wherein: each occurrence of R3 and R3′ is independently hydrogen or an optionally substituted C1-6 aliphatic, wherein: X1, X2, and X3, are each independently N, NR3′, O, S, or CR4, provided that only one of X1, X2, or X3 may be O, S, or NR3′;
each occurrence of R4 is independently hydrogen, —CN, halogen, —Z3—R6, or an optionally substituted group selected from C1-6 aliphatic and 3-10-membered cycloaliphatic, wherein:Z3 is selected from an optionally substituted C1-3 alkylene chain, —O—, —N(R4a)—, —S—, —S(O)—, —S(O)2—, —C(O)—, —CO2—, —C(O)NR4a—, —N(R4a)C(O)—, —N(R4a)CO2—, —S(O)2NR4a—, —N(R4a)S(O)2—, —OC(O)N(R4a)—, —N(R4a)C(O)NR4a—, —N(R4a)S(O)2N(R4a)—, and —OC(O)—;R4a is hydrogen or an optionally substituted C1-4 aliphatic, andR6 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;
or wherein two adjacent occurrences of R3′ or R4, taken together with the atom to which they are bound, form an optionally substituted fused group selected from 5-6-membered aryl and 5-6-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 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, 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, and 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, and sulfur, 6-10-membered aryl, or 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;each occurrence of R12c is independently 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, 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 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—; T2 is an optionally substituted C1-C6 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 C1-4 aliphatic group; n is 0 to 4; W is —C(R7)2—, wherein:
each occurrence of R7 is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, 6-10-membered aryl, 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, —N(R7b)2, —OR7a, —SR7a, halo, and —CN;each occurrence of R7a is independently hydrogen or optionally substituted C1-6 aliphatic or optionally substituted C3-6 cycloaliphatic; each occurrence of R7b is independently hydrogen, optionally substituted C1-6 aliphatic, optionally substituted C3-6 cycloaliphatic, —C(O)R7a, —C(O)OR7a, S(O)R7a, or —S(O)2R7a; or
wherein any two occurrences of R7, R7a, or R7b, taken together with the atom to which they are bound, form an optionally substituted group selected from a 3-6-membered cycloaliphatic ring, 6-10-membered aryl, 3-6-membered heterocyclyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;or wherein any two occurrences of R7a and R2, or R7b and R2 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, and sulfur, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; G1 is —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, andR9 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 HY is an optionally substituted group selected from: wherein each occurrence of X4, X5, X6, and X7 is independently —CR10 or N, provided no more than two occurrences of X4, X5, X6, and X7 are N; each occurrence of Q1 and Q2 is independently S, O or —NRS; each occurrence of Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, and Y9 is independently —CR10 or N, provided no more than two occurrences of Y6, Y7, Y8, and Y9 are 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, and 5-6-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R10 is —R10b, —V1—R10c, -T1-R10b, or —V1-T1-R10b wherein:
V1 is —NR11—, —NR11—C(O)—, —NR11—C(S)—, —NR11—C(NR11)—, —NR11C(O)OR10a—, —NR11C(O)NR11—, —NR11C(O)SR10a—, —NR11C(S)OR10a—, —NR11C(S)NR11—, —NR11C(S)SR10a—, —NR11C(NR11)OR10a—, —NR11C(NR11)NR11—, —NR11S(O)2—, —NR11S(O)2NR11—, —C(O)—, —CO2—, —C(O)NR11—, —C(O)NR11O—, —SO2—, or —SO2NR11—;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, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;T1 is an optionally substituted C1-C6 alkylene chain wherein the alkylene chain optionally is interrupted by —N(R11)—, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —C(O)N(R11)—, —S(O)2N(R11)—, —OC(O)N(R11)—, —N(R11)C(O)—, —N(R11)SO2—, —N(R11a)C(O)O—, —NR10aC(O)N(R10a)—, —N(R10a)S(O)2N(R10a)—, —OC(O)—, or —C(O)N(R11)—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(R11)2, —OR10a, —SR10a, —S(O)2R10a, —C(O)R10a, —C(O)OR10a, —C(O)N(R11)2, —S(O)2N(R11)2, —OC(O)N(R11)2, —N(R11)C(O)R10a, —N(R11)SO2R10a, —N(R11)C(O)OR10a, —N(R11)C(O)N(R11)2, or —N(R11)SO2N(R11)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, 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 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, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, orR10a 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, and sulfur; each occurrence of R11 is independently hydrogen, —C(O)R11a—CO2R11a, —C(O)N(R11a)2, —C(O)N(R11a)—OR11a, SO2R11a, —SO2N(R11a)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, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
wherein each occurrence of R11a 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 R5 is independently hydrogen, —C(O)R5a, —CO2R5a, —C(O)N(R5b)2, —SO2R5a, —SO2N(R5b)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, and sulfur, 6-10-membered aryl, and 5-10-membered heteroaryl having 1-5 heteratoms independently selected from nitrogen, oxygen, and sulfur;
wherein each occurrence of R5a 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 heteratoms independently selected from nitrogen, oxygen, and sulfur; wherein each occurrence of R5b 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 heteratoms independently selected from nitrogen, oxygen, and sulfur; or two occurrences of R5b 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, and sulfur, and 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. |
