Substituted phenyl compounds as endothelin antagonists

Details Substituted phenyl compounds as endothelin antagonists Substituted phenyl compounds as endothelin antagonists

C - Chemistry, Metallurgy

07

D

C07D 213/57 (2006.01) A61K 31/275 (2006.01) A61K 31/335 (2006.01) A61K 31/38 (2006.01) A61K 31/41 (2006.01) A61K 31/435 (2006.01) A61K 31/495 (2006.01) C07C 255/54 (2006.01) C07D 213/30 (2006.01) C07D 213/61 (2006.01) C07D 231/12 (2006.01) C07D 237/08 (2006.01) C07D 239/26 (2006.01) C07D 261/08 (2006.01) C07D 263/56 (2006.01) C07D 271/06 (2006.01) C07D 275/02 (2006.01) C07D 277/24 (2006.01) C07D 277/30 (2006.01) C07D 307/12 (2006.01) C07D 307/54 (2006.01) C07D 317/54 (2006.01) C07D 317/60 (2006.01) C07D 333

Patent

CA 2211646

Compounds of formula (I) are described, wherein: R1 is CN, CH2CN, CH=CHCN, CHO, or CH=CHCO2H; R2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio in which each of the aryl and heteroaryl moieties is optionally substituted; R3 is halogen; R4 is optionally substituted aryl or optionally substituted heteroaryl; R5 is carboxy or an acid isostere; X is oxygen or sulphur; and n is zero or 1; and their N-oxides and prodrugs, and pharmaceutically acceptable salts thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.

L'invention porte sur des composés de la formule (I), leurs oxydes d'azote, leurs précurseurs de médicament ainsi que les sels acceptables du point de vue pharmaceutique qui en sont issus. Dans cette formule, R<1> est CN, CH2CN, CH=CHCN, CHO, ou CH=CHCO2H; R<2> est aryle alcoxy inférieur, hétéroaryle alcoxy inférieur, aryle alkylthio inférieur ou hétéroaryle alkylthio inférieur, dans lequel chacun des fragments aryle ou hétéroaryle peut, éventuellement, être substitué; R<3> est halogène; R<4> est éventuellement aryle substitué ou hétéroaryle substitué; R<5> est carboxy ou un isostère acide; X est oxygène ou soufre et n vaut zéro ou 1. Ces composés, qui ont une activité antagoniste de celle de l'endothéline, ont montré leur efficacité en tant que préparations pharmaceutiques

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