Endothelin receptor antagonists

A compound of Formula (I):

• ##STR48## wherein (Z) is ##STR49## P is CO.sub.2 R.sub.6 or C(O)N(R.sub.6)S(O).sub.q R.sub.10 ;
• R.sup.a is independently hydrogen or C.sub.1-6 alkyl;
• R.sub.1 is independently hydrogen, Ar, C.sub.1-6 alkyl or C.sub.1-5 alkoxy;
• R.sub.2 is ##STR50## R.sub.3 and R.sub.5 are independently R.sub.13 OH, C.sub.1-8 alkoxy, S(O).sub.q R.sub.11, N(R.sub.6).sub.2, NO.sub.2, Br, F, I, Cl, CF.sub.3, NHCOR.sub.6, R.sub.13 CO.sub.2 R.sub.7, --X--R.sub.9 --Y, --X(C(R.sub.6).sub.2)OR.sub.6, --(CH.sub.2).sub.m X'R.sub.8 or --X(CH.sub.2).sub.n R.sub.8 wherein each methylene group within --X(CH.sub.2).sub.n R.sub.8 may be unsubstituted or substituted by one or two --(CH.sub.2).sub.n Ar groups;
• R.sub.4 is independently R.sub.11, OH, C.sub.15 alkoxy, S(O).sub.q R.sub.11, N(R.sub.6).sub.2, Br, F, I, Cl or NHCOR.sub.6, wherein the C.sub.1-5 alkoxy may be unsubstituted or substituted by OH, methoxy or halogen;
• R.sub.6 is independently hydrogen or C.sub.1-8 alkyl;
• R.sub.7 is independently hydrogen, C.sub.1-10 alkyl, C.sub.2-10 alkenyl or C.sub.2-8 alkynyl, all of which may be unsubstituted or substituted by one of more OH, N(R.sub.6).sub.2, CO.sub.2 R.sub.12, halogen or XC.sub.1-10 alkyl;
• or R.sub.7 is (CH.sub.2).sub.n Ar;
• R.sub.8 is independently R.sub.11, CO.sub.2 R.sub.7, CO.sub.2 C(R.sub.11).sub.2 O(CO)XR.sub.7, PO.sub.3 (R.sub.7).sub.2, SO.sub.2 NR.sub.7 R.sub.11, NR.sub.7 SO.sub.2 R.sub.11, CONR.sub.7 SO.sub.2 R.sub.11, SO.sub.3 SO.sub.2 R.sub.7, SO.sub.2 R.sub.7, P(O)(OR.sub.7)R.sub.7, CN, CO.sub.2 (CH.sub.2).sub.m C(O)N(R.sub.6).sub.2, C(R.sub.11).sub.2 N(R.sub.7).sub.2, C(O)N(R.sub.6).sub.2, NR.sub.7 C(O)NR.sub.7 SO.sub.2 R.sub.11, OR.sub.6, or tetrazole which is substituted or unsubstituted by C.sub.1-6 alkyl;
• R.sub.9 is independently a bond, C.sub.1-10 alkylene, C.sub.1-10 alkenylene, C.sub.1-10 alkylidene, C.sub.1-10 alkynylene, all of which may be linear or branched, or phenylene, all of which may be unsubstituted or substituted by one of more OH, N(R.sub.6).sub.2, COOH or halogen;
• R.sub.10 is independently C.sub.1-10 alkyl, N(R.sub.6).sub.2 or Ar;
• R.sub.11 is independently hydrogen, Ar, C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, all of which may be substituted or unsubstituted by one or more OH, CH.sub.2 OH, N(R.sub.6).sub.2, or halogen;
• R.sub.12 is independently hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-7 alkynyl;
• R.sub.13 is independently divalent Ar, C.sub.1-10 alkylene, C.sub.1-10 alkylidene, C.sub.2-10 alkenylene, all of which may be unsubstituted or substituted by one or more OH, CH.sub.2 OH, N(R.sub.6).sub.2 or halogen;
• R.sub.14 is independently hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl, Ar or XAr;
• R.sub.15 is independently hydrogen, Ar, C.sub.1-6 alkyl, or XAr;
• R.sub.16 is independently C.sub.1-6 alkyl or phenyl substituted by one or more C.sub.1-6 alkyl, OH,
• C.sub.1-5 alkoxy, S(O).sub.q R.sub.6, N(R.sub.6).sub.2, Br, F, I, Cl, CF.sub.3 or NHCOR.sub.6 ;
• X is independently (CH.sub.2).sub.n, O, NR.sub.6 or S(O).sub.q ;
• X' is independently O, NR.sub.6 or S(O).sub.q ;
• Y is independently CH.sub.3 or X(CH.sub.2).sub.n Ar;
• Ar is;
• ##STR51## naphthyl;
• all of which may be unsubstituted or substituted by one or more Z.sub.1 or Z.sub.2 groups;
• A is independently C.dbd.O, or (C(R.sub.6).sub.2).sub.m ;
• B is independently --CH.sub.2 -- or --O--;
• Z.sub.1 and Z.sub.2 are independently hydrogen, XR.sub.6, C.sub.1-8 alkyl, (CH.sub.2).sub.q CO.sub.2 R.sub.6, C(O)N(R.sub.6).sub.2, CN, (CH.sub.2).sub.n OH, NO.sub.2, F, Cl, Br, I, N(R.sub.6).sub.2, NHC(O)R.sub.6, O(CH.sub.2).sub.m C(O)NR.sub.a SO.sub.2 R.sub.16, (CH.sub.2).sub.m OC(O)NR.sub.a SO.sub.2 R.sub.16, O(CH.sub.2).sub.m NR.sub.a C(O)NR.sub.a SO.sub.2 R.sub.16 tetrazolyl which may be substituted or unsubstituted by C.sub.1-6 alkyl, CF.sub.3 or C(O)R.sub.6 ;
• m is independently 1 to 3;
• n is independently 0 to 6;
• q is independently 0, 1 or 2;
• provided R.sub.3, R.sub.4 and R.sub.5 are not O--O(CH.sub.2).sub.n Ar or O--OR.sub.6 ;
• or a pharmaceutically acceptable salt thereof.