Substituted quinoxaline carboxylic acids for the inhibition of PASK

摘要

Disclosed herein are substituted quinoxaline carboxylic acids of Formula (I):;
and compositions thereof, which may be useful as inhibitors of PAS Kinase (PASK) activity in a human or animal for the treatment of diseases such as diabetes mellitus.

主权项

1. A compound chosen from
2-(Benzofuran-3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(1H-pyrazol-4-yl)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(6-methoxypyridin-3-yl)quinoxaline-6-carboxylic acid, 2-(1H-Indazol-6-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(1-methyl-1H-indazol-6-yl)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(5-methoxy-1H-indol-2-yl)quinoxaline-6-carboxylic acid, 2-(5-Bromopyridin-3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(1H-Indazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)quinoxaline-6-carboxylic acid, 2-(6-(tent-Butoxycarbonylamino)pyridin-3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(2-Fluoropyridin-4-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(6-(pyrrolidin-1-yl)pyridin-3-yl)quinoxaline-6-carboxylic acid, 2-(6-Fluoropyridin-3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, (S)-2-(Benzofuran-2-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(Benzofuran-2-yl)-3-(cyclopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(6-Aminopyridin-3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(5-methoxybenzofuran-2-yl)quinoxaline-6-carboxylic acid, 2-(5-Fluorobenzofuran-2-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(5-Chlorobenzofuran-2-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(Chroman-6-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(Benzo[d]oxazol-2-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(Benzo[b]thiophen-2-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(5-Fluorobenzo[b]thiophen-2-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(1-methyl-1H-indazol-5-yl)quinoxaline-6-carboxylic acid, 2-(1-Ethyl-1H-indazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(1-Benzofuran-2-yl)-3-(diethylamino)quinoxaline-6-carboxylic acid, 2-(6-Fluoro-1-benzofuran-2-yl)-3-[(2S)-2-methylpiperidin-1-yl]quinoxaline-6-carboxylic acid, 3-(Cyclopropyl(methyl)amino)-2-(1H-indazol-5-yl)quinoxaline-6-carboxylic acid, 2-(1-Benzofuran-5-yl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 2-(6-Chloro-1-benzofuran-2-yl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, (S)-2-(6-Fluorobenzofuran-2-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(5,6-Difluorobenzofuran-2-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, (S)-2-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(1H-Indazol-5-yl)-3-(piperidin-1-yl)quinoxaline-6-carboxylic acid, 3-(Azepan-1-yl)-2-(1H-indazol-5-yl)quinoxaline-6-carboxylic acid, 3-(Azepan-1-yl)-2-(1H-indol-5-yl)quinoxaline-6-carboxylic acid, 3-(Diethylamino)-2-(1H-indol-5-yl)quinoxaline-6-carboxylic acid, 3-(Azepan-1-yl)-2-(5-fluorobenzofuran-2-yl)quinoxaline-6-carboxylic acid, (S)-2-(1H-Indol-5-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, (S)-2-(5-Fluorobenzofuran-2-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(1H-pyrazol-5-yl)quinoxaline-6-carboxylic acid, 2-(3-Methyl-1H-indazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(6-Fluoro-1-benzofuran-2-yl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(quinolin-6-yl)quinoxaline-6-carboxylic acid, 2-(1H-Indazol-5-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid, 3-(Azepan-1-yl)-2-(6-fluoro-1-benzofuran-2-yl)quinoxaline-6-carboxylic acid, 3-(Cyclopropyl(methyl)amino)-2-(6-fluorobenzofuran-2-yl)quinoxaline-6-carboxylic acid, 2-(1,2-Benzoxazol-5-yl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 3-(Azepan-1-yl)-2-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(4-phenylfuran-2-yl)quinoxaline-6-carboxylic acid, 2-(Benzo[b]thiophen-2-yl)-3-(piperidin-1-yl)quinoxaline-6-carboxylic acid, 3-(Azepan-1-yl)-2-(benzo[b]thiophen-2-yl)quinoxaline-6-carboxylic acid, (S)-2-(5-Fluorobenzo[b]thiophen-2-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(Benzo[d]thiazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(1,3-Benzothiazol-5-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid, 2-(1,3-Benzothiazol-2-yl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 2-(1,3-Benzothiazol-2-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2,7′-biquinoxaline-6-carboxylic acid, 3-[Cyclopropyl(methyl)amino]-2-(5-fluoro-1-benzofuran-2-yl)quinoxaline-6-carboxylic acid, 2-(5-Fluoro-1-benzofuran-2-yl)-3-(pyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(1H-Benzo[d]imidazol-1-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-[Cyclopropyl(methyl)amino]-2-(1H-indol-5-yl)quinoxaline-6-carboxylic acid, 2-(1H-Indol-5-yl)-3-(piperidin-1-yl)quinoxaline-6-carboxylic acid, (S)-2-(1H-Indol-5-yl)-3-(3-methylmorpholino)quinoxaline-6-carboxylic acid, 2-(1H-Indol-5-yl)-3-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]quinoxaline-6-carboxylic acid, 2-(5-Fluoro-1-benzofuran-2-yl)-3-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]quinoxaline-6-carboxylic acid, (S)-3-(sec-Butyl(methyl)amino)-2-(5-fluorobenzofuran-2-yl)quinoxaline-6-carboxylic acid, 2-(1-Benzofuran-2-yl)-3-[(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-[5-(trifluoromethyl)-1-benzofuran-3-yl]quinoxaline-6-carboxylic acid, 2-(1-Benzofuran-3-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid, (S)-2-(1H-Indol-5-yl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid, (R)-3-(sec-Butyl(methyl)amino)-2-(5-fluorobenzofuran-2-yl)quinoxaline-6-carboxylic acid, 2-(2-Methyl-1H-indol-5-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(2-methyl-1H-indol-5-yl)quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(5-phenylfuran-2-yl)quinoxaline-6-carboxylic acid, 2-(Furan-3-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(4-phenylfuran-2-yl)quinoxaline-6-carboxylic acid,3-[(2S)-2-methylpyrrolidin-1-yl]-2-(1H-pyrrol-3-yl)quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(1H-pyrrol-3-yl)quinoxaline-6-carboxylic acid, 2-(1-Benzofuran-3-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(3-phenylfuran-2-yl)quinoxaline-6-carboxylic acid, 2-[5-(4-Fluorophenyl)furan-2-yl]-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(3-methyl-1-benzofuran-5-yl)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(3-methyl-1H-indol-5-yl)quinoxaline-6-carboxylic acid, (R)-2-(Benzo[d][1,3]dioxol-5-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, (S)-2-(2-Methyl-1H-indol-5-yl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid, 3-[Cyclopropyl(methyl)amino]-2-(2-methyl-1H-indol-5-yl)quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(1-methyl-1H-pyrazol-4-yl)quinoxaline-6-carboxylic acid, 3-[Methyl(propan-2-yl)amino]-2-(1-phenyl-1H-pyrazol-4-yl)quinoxaline-6-carboxylic acid, (S)-2-(1H-indazol-5-yl)-3-(2-methyl-4-(pyridin-2-yl)piperazin-1-yl)quinoxaline-6-carboxylic acid, (S)-7-Hydroxy-2-(1H-indazol-5-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(1H-Benzo[d][1,2,3]triazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)quinoxaline-6-carboxylic acid, (S)-2-(1H-Benzo[d][1,2,3]triazol-5-yl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 3-(Benzyl(methyl)amino)-2-(1H-indazol-5-yl)quinoxaline-6-carboxylic acid, (S)-2-(1H-Indazol-5-yl)-3-(methyl(1-phenylethyl)amino)quinoxaline-6-carboxylic acid, (S)-2-(2-Methyl-1H-indol-5-yl)-3-(2-methyl-4-(pyridin-2-yl)piperazin-1-yl)quinoxaline-6-carboxylic acid, (S)-2-(5-Fluorobenzofuran-2-yl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid, (R)-2-(4-Fluorophenyl)-3-(2-(trifluoromethyl)pyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(methyl(tetrahydro-2H-pyran-4-yl)amino)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(methyl(piperidin-4-yl)amino)quinoxaline-6-carboxylic acid, (S)-3-(sec-Butyl(methyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, (S)-2-(4-Fluorophenyl)-3-(3-methylmorpholino)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-[(2R)-2-(trifluoromethyl)piperidin-1-yl]quinoxaline-6-carboxylic acid, 3-(tert-Butyl(methyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(Cyclohexyl(methyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(methyl(o-tolyl)amino)quinoxaline-6-carboxylic acid, 3-(tert-Butylamino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(Ethyl(isopropyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-[Cyclohexyl(ethyl)amino]-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(Diethylamino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-[(2S)-2-methylpiperazin-1-yl]quinoxaline-6-carboxylic acid, (S)-2-(2,4-Difluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, (S)-2-(2,4-Difluorophenyl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid, (S)-2-(4-Fluoro-2-methylphenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(4-Fluoro-2-methylphenyl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(4-Carbamoylphenyl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-7-hydroxy-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylic acid, (R)-2-(4-Fluorophenyl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-7-methoxy-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 7-Fluoro-2-(4-fluorophenyl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-[methyl(2,2,2-trifluoroethyl)amino]quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(((1r,4r)-4-hydroxycyclohexyl)(methyl)amino)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(methyl((1r,4r)-4-(methylamino)cyclohexyl)amino)quinoxaline-6-carboxylic acid, 3-(((1r,4r)-4-Acetamidocyclohexyl)(methyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(4-Acetylpiperazin-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(4-Benzoylpiperazin-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(4-(methylsulfonyl)piperazin-1-yl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-[4-(pyridin-2-yl)piperidin-1-yl]quinoxaline-6-carboxylic acid, (S)-2-(4-Fluorophenyl)-7-hydroxy-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 3-[Benzyl(methyl)amino]-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-[methyl(pyridin-2-ylmethyl)amino]quinoxaline-6-carboxylic acid, 3-(Cyclopentyl(methyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(Isopropyl(methyl)amino)-2-(4-(trifluoromethyl)phenyl)quinoxaline-6-carboxylic acid, 3-[(1-Ethylpiperidin-4-yl)(methyl)amino]-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, (S)-3-(4-Ethyl-2-methylpiperazin-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-[Ethyl(propyl)amino]-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(Dipropylamino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(isobutyl(methyl)amino)quinoxaline-6-carboxylic acid, 3-(2-Ethylpiperidin-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, (S)-2-(4-Fluorophenyl)-3-(methyl(1-phenylethyl)amino)quinoxaline-6-carboxylic acid, 2-(4-Fluorophenyl)-3-(pyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 3-(Azetidin-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 3-(Cyclobutyl(methyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid, 2-(2,4-Difluorophenyl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, (S)-2-(3,4-Difluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid, 2-(4-Acetamidophenyl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid, and (R)-2-(4-Fluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid.