Phenyl derivatives useful as endothelin receptor antagonists

A compound of Formula (I):

• ##STR14## wherein:
• R is a group Ar as defined hereinafter;
• R.sup.1 is hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, X(CH.sub.2).sub.p Ar;
• or a methylenedioxy group attached to two adjacent ring carbon atoms;
• R.sup.2 is --(CH.sub.2).sub.x CO.sub.2 R.sup.4 ;
• R.sup.3 is X(CH.sub.2)pAr or --X(CH.sub.2)pR.sup.4 or a group of formula (a):
• ##STR15## Ar is a group of formula (b) or (c):
• ##STR16## A is C.dbd.O, or (C(R.sup.4).sub.2).sub.m ;
• each B is independently --CH.sub.2 -- or --O--;
• R.sup.4 is C.sub.1-6 alkyl;
• R.sup.5 is hydrogen or C.sub.1-10 alkyl or Ar, both of which may be unsubstituted or substituted by one or two Cl, F, Br, hydroxy, --XC.sub.1-5 alkyl, C.sub.1-5 alkyl, NO.sub.2, or R.sup.5 is --N(R.sup.4).sub.2 ;
• R.sup.6 is hydrogen, R.sup.10, CO.sub.2 R.sup.11, CO.sub.2 C(R.sup.10).sub.2 O(CO)XR.sup.11, PO.sub.3 (R.sup.11).sub.2, SO.sub.2 NR.sup.11 R.sup.10, NR.sup.11 SO.sub.2 R.sup.10, CONR.sup.11 SO.sub.2 R.sup.10, SO.sub.3 R.sup.11, S(O).sub.q R.sup.11, S(O).sub.q N(R.sup.11)C(O)R.sup.10, S(O).sub.q N(R.sup.11)S(O).sub.q R.sup.10, C(O)N(R.sup.11)C(O)R.sup.10, N(R.sup.11)C(O)R.sup.10, N(R.sup.11).sub.2, N(R.sup.11)C(O)NR.sup.11, P(O)(OR.sup.11)R.sup.11, CN, --CO.sub.2 (CH.sub.2).sub.m C(O)N(R.sup.4).sub.2, C(R.sup.10).sub.2 N(R.sup.11).sub.2, C(O)N(R.sup.4).sub.2, or OR.sup.4 ;
• R.sup.7 and R.sup.9 are independently hydrogen, R.sup.10, OH, C.sub.1-8 alkoxy, S(O).sub.q R.sup.10, N(R.sup.4).sub.2, Br, F, I, Cl, CF.sub.3, NO.sub.2, NHCOR.sup.4, R.sup.12 CO.sub.2 R.sup.11, --X--R.sup.13 --Y, --X(CR.sup.4)pOR.sup.4, S(CH.sub.2)pCO.sub.2 H, (CH.sub.2)pX--R.sup.13 --X(CH.sub.2)pCONR.sup.11 SO.sub.2 R.sup.10, (CH.sub.2)pXCONR.sup.11 SO.sub.2 R.sup.10, or --X(CH.sub.2).sub.p R.sup.6 wherein each methylene group within --X(CH.sub.2).sub.p R.sup.6 may be unsubstituted or substituted by one or two --(CH.sub.2).sub.p Ar groups;
• R.sup.8 is hydrogen, R.sup.10, OH, C.sub.1-5 alkoxy, S(O).sub.q R.sup.10, N(R.sup.4).sub.2, Br, F, I, Cl or NHCOR.sup.4 wherein the C.sub.1-5 alkoxy may be unsubstituted or substituted by OH, methoxy or halogen;
• R.sup.10 is hydrogen, Ar, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, all of which may be unsubstituted or substituted by one or more OH, CH.sub.2 OH, N(R.sup.4).sub.2 or halogen, or R.sup.10 is N(R.sup.4).sub.2 ;
• R.sup.11 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 or more OH, N(R.sup.4).sub.2, CO.sub.2 R.sup.14, halogen or XC.sub.1-5 alkyl;
• or R.sup.11 is (CH.sub.2).sub.p Ar;
• R.sup.12 is divalent Ar, C.sub.1-10 alkylene, C.sub.1-10 alkylidene, C.sub.2-10 alkenylene, C.sub.2-10 -alkynylene, all of which may be unsubstituted or substituted by one or more OH, CH.sub.2 OH, N(R.sup.4).sub.2 or halogen;
• R.sup.13 is 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 or more OH, N(R.sup.4).sub.2, COOH or halogen;
• R.sup.14 is hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-7 alkynyl;
• X is (CH.sub.2).sub.p, O, NR.sup.4 or S(O).sub.q ;
• Y is CH.sub.3 or X(CH.sub.2).sub.p Ar;
• q is zero, one or two;
• p is an integer from 0 to six;
• m is 1, 2 or 3;
• n is 1 to 4;
• x is 0 to 4;
• y is 1 to 2;
• the dotted line signifies the optional presence of a bond such that .dbd. represents a single or double bond;
• or a pharmaceutically acceptable salt thereof.