US 8,012,989 B2 · Substituted pyrimidine compounds and their utility as CETP inhibitors

Abstract

A compound represented by the following general formula (I), wherein R1, R2, R3, R4 and R5 represent hydrogen atom, a halogen atom, a lower alkyl group and the like, R6 represents an alkyl group, a cycloalkyl group and the like, R7 and R8 represent hydrogen atom, a lower alkyl group, a (lower cycloalkyl)(lower alkyl) group and the like, R9 represents hydrogen atom, a halogen atom, a lower alkoxy group and the like, R10 and R11 represent hydrogen atom, a lower alkyl group, a lower alkoxy group, a halo(lower alkyl) group and the like, and A represents a heterocyclic ring constituted by 6 to 10 atoms, which has potent inhibitory activity on cholesterol ester transfer protein (CETP).

A compound which is:

N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylsulfinyl)ethoxy]pyrimidin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl) (ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{-[5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethylquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethylquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethyl-6-methoxyquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethyl-6-methoxyquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethyl-6-trifluoromethylquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethyl-6-trifluoromethylquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethyl-6-methylquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl {5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethyl-6-methylquinolin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-([2-[(cyclopentylmethyl)(ethyl)amino]-6-methylpyridin-3-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-6-methylpyridin-3-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-6-ethylpyridin-3-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-6-ethylpyridin-3-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino)-5,6-dimethylpyridin-3-yl]methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5,6-dimethylpyridin-3-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]propyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethylquinolin-2-amine,
3-[({1-[3,5-bis(trifluoromethyl)phenyl]propyl}{5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-yl}amino)methyl]-N-(cyclopentylmethyl)-N-ethylquinolin-2-amine,
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]pyrazin-2-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine, or
N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]pyrazin-2-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine, or
at least one enantiomer, mixtures of enantiomers, or a pharmaceutically acceptable salt thereof.

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Substituted pyrimidine compounds and their utility as CETP inhibitors

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Substituted pyrimidine compounds and their utility as CETP inhibitors

Life of this patent

Abstract

Claims2