Carboxamide compounds and methods for using the same

摘要

Disclosed are carboxamide compounds, as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure;
in which R1, R2, R3, R4, D, J, Z, T, p, q, w and x are as described herein. In certain embodiments, a compound disclosed herein activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.

主权项

1. A compound having the structural formula or a pharmaceutically acceptable salt or N-oxide thereof, wherein
R1 is H, —(C1-C4 alkyl), —C(O)—(C1-C4 alkyl) or —C(O)O—(C1-C4 alkyl);each R15 is independently selected from —(C1-C3 alkyl), —(C1-C3 haloalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)-NR8R9, —(C0-C3 alkyl)-OR10, —(C0-C3 alkyl)-C(O)R10, —(C0-C3 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN and two R15 on the same carbon optionally combine to form oxo;v is 0, 1, 2, 3 or 4;G is —S(O)2—, L, or —(C0-C3 alkyl)-, in which each carbon of the —(C0-C3 alkyl)- is optionally and independently substituted with one or two R16;R17 is aryl or heteroaryl, optionally substituted with 1, 2 or 3 substituents independently selected from —(C1-C3 alkyl), —(C1-C3 haloalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)-NR8R9, —(C0-C3 alkyl)-OR10, —(C0-C3 alkyl)-C(O)R10, —(C0-C3 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN;each R3 is independently selected from —(C1-C3 alkyl), —(C1-C3 haloalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)-NR8R9, —(C0-C3 alkyl)-OR10, —(C0-C3 alkyl)-C(O)R10, —(C0-C3 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN;w is 0, 1, 2 or 3;J is —C(O)— or —N(R38)—C(O)—, in which R38 is independently selected from —H, —(C1-C4 alkyl), —C(O)—(C1-C4 alkyl) and —C(O)O—(C1-C4 alkyl);each R4 is independently selected from —(C1-C3 alkyl), —(C1-C3 haloalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)-NR8R9, —(C0-C3 alkyl)-OR10, —(C0-C3 alkyl)-C(O)R10, —(C0-C3 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN, and two R4 groups optionally combine to form an oxo;x is 0, 1, 2, 3 or 4;Q is —S(O)2—, L, or —(C0-C3 alkyl)-, in which each carbon of the —(C0-C3 alkyl)- is optionally and independently substituted with one or two R16; the ring denoted by “A” is heteroaryl or aryl; each R5 is independently selected from —(C1-C3 alkyl), —(C1-C3 haloalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)-NR8R9, —(C0-C3 alkyl)-OR10, —(C0-C3 alkyl)-C(O)R10, —(C0-C3 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN;
y is 0, 1, 2, 3 or 4;in which
each L is independently selected from —NR9C(O)O—, —OC(O)NR9—, —NR9C(O)—NR9—, —NR9C(O)S—, —SC(O)NR9—, —NR9C(O)—, —C(O)—NR9—, —NR9C(S)O—, —OC(S)NR9—, —NR9C(S)—NR9—, —NR9C(S)S—, —SC(S)NR9—, —NR9C(S)—, —C(S)NR9—, —SC(O)NR9—, —NR9C(S)—, —S(O)0-2—, —C(O)O, —OC(O)—, —C(S)O—, —OC(S)—, —C(O)S—, —SC(O)—, —C(S)S—, —SC(S)—, —OC(O)O—, —SC(O)O—, —OC(O)S—, —SC(S)O—, —OC(S)S—, —NR9SO2—, —SO2NR9— and —NR9SO2NR9—,each R7, R8 and R10 is independently selected from H, —(C1-C2 alkyl), —(C1-C2 haloalkyl), —(C0-C2 alkyl)-L-(C0-C2 alkyl), —(C0-C2 alkyl)-NR9(C0-C2 alkyl), —(C0-C2 alkyl)-O—(C0-C2 alkyl), —(C0-C2 alkyl)-C(O)—(C0-C2 alkyl) and —(C0-C2 alkyl)-S(O)0-2—(C0-C2 alkyl),each R9 is independently selected from —H, —(C1-C4 alkyl), —C(O)—(C1-C4 alkyl) and —C(O)O—(C1-C4 alkyl), andeach R16 is independently selected from —(C1-C3 alkyl), —(C1-C3 haloalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)-NR8R9, —(C0-C3 alkyl)—OR10, —(C0-C3 alkyl)-C(O)R10, —(C0-C3 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN, and two R16 on the same carbon optionally combine to form an oxo.