1-CYCLOALKYL- OR 1-HETEROCYCLYL-HYDROXYIMINO-3-PHENYL-PROPANES

摘要

This invention relates to novel 1-cycloalkyl- or 1-heterocyclyl-hydroxyimino-3-phenyl-propanes of the formula;wherein R1 to R7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

主权项

1. A compound of formula I, wherein R1 is C4-7-cycloalkyl, said cycloalkyl being unsubstituted or substituted by one, two or three groups independently selected from the group consisting of C1-7-alkyl, hydroxy, oxo, dioxo and C1-7-alkylcarbonyl; or heterocyclyl, said heterocyclyl having 4 to 7 ring atoms, comprising one, two or three heteroatoms selected from N, O and S and being unsubstituted or substituted by one, two or three groups independently selected from the group consisting of C1-7-alkyl, hydroxy, oxo, dioxo, and C1-7-alkylcarbonyl; R2 is selected from the group consisting of C1-7-alkyl, C3-7-cycloalkyl, C2-7-alkenyl, halogen-C1-7-alkyl, unsubstituted phenyl or phenyl substituted by one, two or three groups independently selected from the group consisting of C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxy and C1-7-alkylsulfonyl, and heteroaryl, said heteroaryl being unsubstituted or substituted by C1-7-alkyl or oxo, R3 and R7 are independently from each other selected from the group consisting of hydrogen, halogen and C1-7-alkyl; and R4, R5 and R6 are independently selected from the group consisting of hydrogen, halogen, halogen-C1-7-alkyl, cyano, cyano-C1-7-alkyl, C1-7-alkyl, C1-7-alkenyl, C1-7-alkynyl, C1-7-alkoxy, C1-7-alkoxy-C1-7-alkyl, hydroxy, hydroxy-C1-7-alkyl, hydroxy-C3-7-alkenyl, hydroxy-C3-7-alkynyl, hydroxy-C1-7-alkoxy, carboxyl, carboxyl-C1-7-alkyl, caboxyl-C3-7-alkenyl, carboxyl-C1-7-alkynyl, carboxyl-C1-7-alkoxy, tetrazolyl, C1-7-alkoxycarbonyl, C1-7-alkylsulfonyl, C1-7-alkylsulfonyloxy, C1-7-alkylsulfonylamino, C3-7-cycloalkylsulfonylamino, aminosulfonyl, (C1-7-alkyl)-aminosulfonyl, di-(C1-7-alkyl)-aminosulfonyl, heterocyclylsulfonyl, C1-7-alkyl-amino, di-(C1-7-alkyl)-amino, C1-7-alkoxy-C1-7-alkyl-amino, C1-7-alkoxy-C1-7-alkyl-C1-7-alkyl-amino, C1-7-alkoxy-halogen-C1-7-alkyl-amino, hydroxy-C1-7-alkyl-C1-7-alkyl-amino, an amino acid attached through the amino group of the amino acid, C3-7-cycloalkyl-amino, wherein C3-7-cycloalkyl is unsubstituted or substituted by hydroxy, hydroxy-C1-7-alkyl or carboxyl, carboxyl-C1-7-alkyl-aminocarbonyl, carboxyl-C1-7-alkyl-(C1-7-alkyl)aminocarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl-aminocarbonyl, C1-7-alkyl-aminocarbonyl, di-(C1-7-alkyl)-aminocarbonyl, C1-7-alkylsulfonyl-C1-7-alkyl-aminocarbonyl, halogen-C1-7-alkyl-aminocarbonyl, hydroxy-C1-7-alkyl-aminocarbonyl, hydroxy-C1-7-alkyl-C1-7-alkyl-aminocarbonyl, halogen-hydroxy-C1-7-alkyl-aminocarbonyl, C1-7-alkoxy-C1-7-alkyl-aminocarbonyl, C3-7-cycloalkylaminocarbonyl, wherein C3-7-cycloalkyl is unsubstituted or substituted by hydroxy, hydroxy-C1-7-alkyl or carboxyl, heterocyclyl-aminocarbonyl, wherein heterocyclyl is unsubstituted or substituted by C1-7-alkyl or oxo, heterocyclyl-C1-7-alkyl-aminocarbonyl, wherein heterocyclyl is unsubstituted or substituted by C1-7-alkyl or oxo, hydroxy-C1-7-alkyl-aminocarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkyl, di-(C1-7-alkoxycarbonyl)-C1-7-alkyl, C1-7-alkylcarbonylamino-C1-7-alkylaminocarbonyl, C1-7-alkylcarbonylamino, carboxyl-C1-7-alkylcarbonylamino, C1-7-alkoxycarbonyl-C1-7-alkylcarbonylamino, C3-7-cycloalkyl, wherein C3-7-cycloalkyl is unsubstituted or substituted by hydroxy, hydroxy-C1-7-alkyl or carboxyl, C3-7-cycloalkyl-C1-7-alkyl, wherein C1-7-cycloalkyl is unsubstituted or substituted by hydroxy, hydroxy-C1-7-alkyl or carboxyl, heterocyclyl, said heterocyclyl being unsubstituted or substituted by C1-7-alkyl, halogen, hydroxy, hydroxy-C1-7-alkyl, C1-7-alkoxy, oxo, carboxyl, carboxyl-C1-7-alkyl, C1-7-alkoxycarbonyl, aminocarbonyl, C1-7-alkylsulfonyl, aminosulfonyl, C1-7-alkylcarbonyl, carboxyl-C1-7-alkyl-aminocarbonyl or hydroxysulfonyl-C1-7-alkyl-aminocarbonyl, heterocyclylcarbonyl, said heterocyclyl being unsubstituted or substituted by C1-7-alkyl, halogen, hydroxy, hydroxy-C1-7-alkyl, C1-7-alkoxy, oxo, carboxyl, carboxyl-C1-7-alkyl or C1-7-alkylsulfonyl, heteroaryl, said heteroaryl being unsubstituted or substituted by C1-7-alkyl, C3-7-cycloalkyl, tetrahhydropyranyl, carboxyl, carboxyl-C1-7-alkyl, C1-7-alkoxy-C1-7-alkyl or C1-7-alkoxycarbonyl, phenyloxy, wherein phenyl is unsubstituted or substituted by one to three groups selected from halogen or carboxyl, and phenyl, said phenyl being unsubstituted or substituted by one to three groups selected from the group consisting of halogen, C1-7-alkyl, hydroxy, hydroxy-C1-7-alkyl, cyano, cyano-C1-7-alkyl, amino, C1-7-alkoxy, carboxyl, carboxyl-C1-7-alkyl, C1-7-alkoxy-carbonyl, tetrazolyl, carboxyl-C1-7-alkyl-carbonylamino, C1-7-alkoxy-carbonyl-C1-7-alkyl-carbonylamino, C1-7-alkylsulfonyl, C1-7-alkyl-sulfonylamino, aminosulfonyl, C1-7-alkyl-aminosulfonyl, di-(C1-7-alkyl)-aminosulfonyl, heterocyclylsulfonyl, C1-7-alkoxycarbonyl-C1-7-alkoxy, C1-7-alkoxycarbonyl-C1-7-alkyl-aminocarbonyl, carboxyl-C1-7-alkyl-aminocarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl-carbonylamino-C1-7-alkylsulfonyl, phenyl-C1-7-alkyl-aminocarbonyl, tetrazolyl-aminocarbonyl, tetrazolyl-C1-7-alkyl-aminocarbonyl and carboxyl-C1-7-alkyl-aminocarbonyl; or a pharmaceutically acceptable salt thereof.