AMPK-activating piperidinyloxy-substituted 2,3-dihydro-1H-indene-1-amine compounds and pharmaceutical compositions including the same

摘要

Disclosed are carboxamide, sulfonamide and amine compounds including certain AMPK-activating piperidinylxoy-substituted 2,3-dihydro-1H-indene-1-amine compounds, as well as pharmaceutical compositions including them. One embodiment is a compound having the structure;
in which R1, R3,R4,R5,R14,R15,R17, G, Q, k, v, x and y 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 formulaor a pharmaceutically acceptable salt, or N-oxide thereof, wherein
R1 is H; each R15 is independently selected from —(C1-C3 alkyl), —(C1-C3 fluoroalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)—NR8R9, —(C0-C3 alkyl)—OR10, —(C0-C3 alkyl)—(C0-C3alkyl)—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 or 2; G is —CH2—, —C(O)—, —S(O)2— or —CH(CH3)—; and R17 is phenyl, pyridyl, pyrimidinyl or imidazolyl, unsubstituted or substituted with 1, 2 or 3 substituents independently selected from —(C1-C3 alkyl), —(C1-C3 fluoroalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3alkyl)—NR8R9, —(C0-C3 alkyl)—OR10, —(C0-C3alkyl)—C(O)R10, (C0-C3alkyl)—S(O)0-2R10, -halogen, —NO2 and —CN; each R3 is substituted on a benzo and is independently selected from —(C1-C3 alkyl), —(C1-C3 fluoroalkyl), —(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 or 2; each R14 is substituted on a non-benzo carbon of the 2,3-dihydro-1H-indene and is independently selected from —(C1-C3 alkyl), —(C1-C3 fluoroalkyl), —(C0-C3 alkyl)-L-R7, —(C0-C3 alkyl)—NR8R9, —(C0-C3 alkyl)—OR10, —(C0-C3 alkyl)—S(O)0-2R10, -halogen, —NO2 and —CN; k is 0, 1 or 2; each R4 is independently selected from —(C1-C3 alkyl), —(C1-C3 fluoroalkyl), —(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 on the same carbon optionally combine to form oxo; x is 0, 1 or 2; Q is —CH2—, a single bond, —C(O)—, —S(O)2— or —CH(CH3)—; each R5 is independently selected from —(C1-C3 alkyl), —(C1-C3 fluoroalkyl), —(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 y is 0,1,2 or 3; 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—, —NR9C(NR2)NR9—, —NR9SO2—, —SO2NR9—and —NR9SO2NR9—,each R7, R8 and R10 is independently selected from H, —(C1-C2 alkyl) and —(C1-C2 fluoroalkyl), each R9 is independently selected from —H, —(C1-C4 alkyl) and —C(O)O—(C1-C4 alkyl).