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US 9,174,964 B2Granted
AMPK-activating piperidinyloxy-substituted 2,3-dihydro-1H-indene-1-amine compounds and pharmaceutical compositions including the same
AssigneeRigel Pharmaceuticals, Inc.
InventorsHui Hong, Xiang Xu, Jiaxin Yu, Rajinder Singh, Ihab S. Darwish, Sambaiah Thota
Life of this patent
Estimating the term…
Abstract
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.
Claims23
A compound having the structural formula
- or 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).
17 more elements
Dependencies are inferred from the claim text.