NOVEL CARBOXYLIC ACID DERIVATIVES WITH 5,6 SUBSTITUTED PYRIMIDINE RING, THE PRODUCTION AND UTILIZATION THEREOF FOR PRODUCING ENDOTHELIN RECEPTOR ANTAGONISTS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE COMPOUNDS

摘要

The present invention relates to carboxylic acid derivatives of the general formula wherein R1 is a tetrazolyl group or a group in which R a) - OR7 wherein R7 is hydrogen, metal cation, cycloalkyl, alkyl, optionally substituted ammonium ion, -CH2-phenyl, phenyl- , alkenyl, alkynyl, b) an optionally substituted heteroaromatic system; c) wherein k is 0-2, p 1-4, and R 8 1-4 are alkyl, cycloalkyl, alkenyl, alkynyl or optionally substituted phenyl; d) wherein R9 is optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl; R 2 is hydroxy, optionally substituted amino, alkyl, alkenyl, alkynyl, alkoxy, alkylthio or CR 2 together with CR 3 forms an optionally substituted alkylene or alkenylene ring; R3 is halogen, hydroxy, optionally substituted amino, alkyl, alkenyl, alkynyl, alkenyloxy, alkylcarbonyl, alkoxycarbonyl, -NH-O-alkyl, alkylthio, or CR3 forms a ring with CR2; R4 and R5 are cycloalkyl or optionally substituted and optionally linked phenyl or naphthyl; R6 is hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, naphthyl or heteroaromatic ring; and Z are sulfur or oxygen and used as endothelin antagonists in the preparation of pharmaceutical compositions. The invention also relates to pharmaceutical compositions containing the compounds of formula (I). SHE