N-substituted-heterocycloalkyloxybenzamide compounds and methods of use

摘要

The present invention provides N-substituted-heterocycloalkyloxybenzamide compounds, as well as pharmaceutical compositions and methods of use. One embodiment of the invention is a compound having the structure;
in which R1, R2, R3, R4, T, n, w and x are as described herein. In certain embodiments of the invention, a compound of the present invention activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.

主权项

1. A compound having the structural formulaor a pharmaceutically acceptable salt or N-oxide thereof, wherein
each R3 is independently selected from halo, cyano, —(C1-C4 fluoroalkyl), —O—(C1-C4 fluoroalkyl), acyl, carboxylate, carboxamide and nitro; w is 0, 1, 2 or 3; each R4 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), -halogen, —NO2 and —CN, and two R4 on the same carbon optionally combine to form oxo; x is 0, 1, 2, 3 or 4; each R5 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), —(C0-C6 alkyl)-L-R7, —(C0-C6 alkyl)-NR8R9, —(C0-C6 alkyl)-OR10, —(C0-C6 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN; y is 0, 1, 2, 3 or 4; G is a single bond, —CH2— or —C(O)—; v is 0, 1, 2, 3 or 4; each R15 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), -halogen, —NO2 and —CN, and two R15 on the same carbon optionally combine to form oxo; and R17 is optionally-substituted aryl; in which
each L is independently selected
from —NR9C(O)O—, —NR9C(O)—NR9—, —NR9C(O)S—, —NR9C(O)—, —NR9C(S)O—, —NR9C(S)—NR9—, —NR9C(S)S—, —NR9C(S)—, —OC(O)NR9—, —SC(O)NR9—, —C(S)NR9—, —OC(S)NR9—, —SC(S)NR9—, —C(S)NR9—, —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—, —NR9C(NR9)NR9—, —NR9SO2—, —SO2NR9— and —NR9SO2NR9—,each R7, R8 and R10 is independently selected from H, —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), —(C0-C6 alkyl)-L-(C0-C6 alkyl), —(C0-C6 alkyl)-NR9(C0-C6 alkyl), —(C0-C6 alkyl)-O—(C0-C6 alkyl) and —(C0-C6 alkyl)-S(O)0-2—(C0-C6 alkyl),each R9 is independently selected from —H, —(C1-C4 alkyl) and —C(O)—(C1-C4 alkyl), andeach R16 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), and two R16 on the same carbon optionally combine to form oxo; provided that the compound is not
N-(1-benzylpiperidin-4-yl)-3-chloro-4-(1-(4-methoxybenzyl)piperidin-4-yloxy)benzamide;N-(1-benzylpiperidin-4-yl)-4-(1-benzylpiperidin-4-yloxy)-3-methoxybenzamide; orN-(1-benzylpiperidin-4-yl)-3-(1-benzylpiperidin-4-yloxy)benzamide.