Pyrimidyl- or (oxazolyl- or thiazolyl-)oxy substituted carboxylic acid derivatives useful as mixed ETA/ETB endothelin-receptor antagonists

摘要

A carboxylic acid derivative or a physiologically tolerated salts or enantiomerically pure forms thereof has the formula (I) wherein: R is tetrazole or -C(O)-R1; R1 is OR7, cycloalkyl, alkyl, or optionally substituted CH2-phenyl, alkenyl, alkynyl or phenyl; R4 and R5 are independently optionally substituted phenyl or naphthoyl or phenyl or naphthyl which are linked together in the ortho positions by a direct linkage, methylene, ethylene or ethenylene, oxygen, sulphur, SO2, NH or N-alkyl; R6 is H, or optionally substituted alkyl, alkenyl, alkynyl, phenyl, naphthyl, a five or six membered heteroaromatic system comprising one to three nitrogens and/or sulphur or oxygen or cycloalkyl; Z is sulphur or oxygen; B is alkylene; Het is a heterocyclic radical of formula Ia or Ib'; R2 is H, OH, N(R')2, halo, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, alkylthio or CR2 is linked to C10 to form a 5 or 6 membered ring defined below or if Het is a 5 membered ring, CR2 together with CR3 can be an optionally substituted 5- or 6- membered alkenyl or alkylenyl ring; X and Y are independently nitrogen or methane; W is nitrogen or CR10; R10 is H, halo or alkyl or CR10 forms together with CR2 or CR3 an optionally substituted 5 or 6 membered alkylene or alkenylene ring wherein one or more of the methylene groups can be replaced by oxygen, sulphur or NR'; R3 is H, OH, N(R')2, halo, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, halolkoxy, alkylthio or CR3 is linked to C10 to form a 5 or 6 membered ring defined above; R' is H or alkyl; T is O, S or NR8 and R8 is alkyl. A pharmaceutical composition thereof is useful as an endothelin receptor antagonist.