EP2545964A1 — Novel FXR (NR1H4) binding and activity modulating compounds

USPTO Abstract

The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists of the NR1H4 receptor (FXR). The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds and to a process for the synthesis of said compounds. wherein R is selected from the group consisting of COOR 6 , CONR 7 R 8 , tetrazolyl, SO 2 NR 7 R 8 , C 1-6 alkyl, SO 2 -C 1-6 alkyl and H, with R 6 independently selected from the group consisting of H or C 1-6 alkyl, and R 7 and R 8 independently from each other selected from the group consisting of H, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkylene-R 9 , SO 2 -C 1-6 alkyl, wherein R 9 is selected from the group consisting of COOH, OH and SO 3 H; A is selected from the group consisting of phenyl, pyridyl, pyrimidyl, pyrazolyl, indolyl, thienyl, benzothienyl, indazolyl, benzisoxazolyl, benzofuranyl, benzotriazolyl, furanyl, benzothiazolyl, thiazolyl, oxadiazolyl, each optionally substituted with one or two groups independently selected from the group consisting of OH, O-C 1-6 alkyl, O-halo-C 1-6 alkyl, C 1-6 alkyl, halo-C 1-6 alkyl, C 3-6 cycloalkyl and halogen; Q is selected from the group consisting of phenyl, pyridyl, thiazolyl, thiophenyl, pyrimidyl, each optionally substituted with one or two groups independently selected from the group consisting of C 1-6 alkyl, halo-C 1-6 alkyl, halogen and CF 3 ; Y is selected from N or CH; Z is selected from wherein X= CH, N, NO.