Compositions and methods for inhibiting TGF-beta

A compound of formula I:

• 103
• or a pharmaceutically acceptable salt thereof, wherein:
• a-b is CH2CH2, CH2CH2CH2, CH═CH, CH═N, or N═CH, wherein each hydrogen is optionally replaced by a C14 aliphatic group;
• Z is N or C—F;
• G is C1-6 aliphatic or a phenyl, naphthyl, or 5-6 membered heteroaryl ring having 1-3 ring heteroatoms selected from nitrogen, sulfur or oxygen, wherein G is optionally substituted by 1-3 R5;
• Ring A is optionally substituted by 1-3 R1;
• Ring B is optionally substituted by 1-2 R6 at a position ortho to the ring nitrogen and is optionally substituted by R7 at the position meta to the ring nitrogen;
• each R1 is independently selected from —R2, -T-R2, or —V-T-R2;
• each R2 is independently selected from C13 aliphatic, hydroxy, —N(R3)2, halo, cyano, —OR4, —C(O)R4, —CO2R4, —SR4, —S(O)R4, —S(O)2R4, —N(R3)C(O)R4, —N(R3)CO2R4, —N(R3)SO2R4, —C(O)N(R3)2, —SO2N(R3)2, —N(R3)C(O)N(R3)2, —OC(O)R4, phenyl, 5-6 membered heterocyclyl or 5-6 membered heteroaryl;
• each T is independently a C1-5 alkylidene that is optionally interrupted by —O—, —C(O)—, —S—, —S(O)—, —S(O)2—, or —N(R3)—;
• each V is independently selected from —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —N(R3)—, —N(R3)C(O)—, or —N(R3)C(O)2—, —N(R3)S(O)2—, —C(O)N(R3)—, —S(O)2N(R3)—, —N(R3)C(O)N(R3)—, or —OC(O)—;
• each R3 is independently selected from hydrogen, C1-6 aliphatic, —C(O)R4, —C(O)2R4, —SO2R4, or two R3 on the same nitrogen together with their intervening nitrogen form a 5-6 membered heterocyclyl or heteroaryl ring having 1-3 ring heteroatoms selected from nitrogen, oxygen or sulfur;
• each R4 is independently selected from a C1-6 aliphatic group, phenyl or a 5-6 membered heteroaryl or heterocyclyl having 1-3 ring heteroatoms selected from nitrogen, oxygen or sulfur;
• each R5 is independently selected from C1-6 aliphatic, halo, —OH, —N(R3)2, cyano, —OR4, —C(O)R4, —CO2R4, —SR4, —S(O)R4, —S(O)2R4, —N(R3)C(O)R4, —N(R3)CO2R4, —N(R3)SO2R4, —C(O)N(R3)2, —SO2N(R3)2, —N(R3)C(O)N(R3)2, —OC(O)R4, —OC(O)N(R3)2, phenyl, 5-6 membered heterocyclyl or 5-6 membered heteroaryl, or two adjacent R5 on a phenyl, naphthyl or heteroaryl ring are taken together with their intervening atoms to form a 5-6 membered fused ring having 0-2 heteroatoms selected from nitrogen, oxygen or sulfur;
• each R6 is independently selected from a C1-4 alkyl, C1-4 alkoxy, or C1-4 mono- or dialkylamino;
• and
• R7 is selected halo, —OH, —N(R3)2, cyano, —OR4, —C(O)R4, —CO2R4, —SR4, —S(O)R4, —S(O)2R4, —N(R3)C(O)R4, —N(R3)CO2R4, —N(R3)SO2R4, —C(O)N(R3)2, —SO2N(R3)2, —N(R3)C(O)N(R3)2, or —OC(O)R4.