N-(5-isoxazolyl)biphenylsulfonamides, N-(3-isoxazolyl)biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin

A compound of formula I:

• ##STR8## or a pharmaceutically acceptable salt of a compound of formula I, wherein:
• R.sup.1 and R.sup.2 are either (i), (ii) or (iii) as follows:
• (i) R.sup.1 and R.sup.2 are each independently selected from the group consisting of H, NH.sub.2, NO.sub.2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido and substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms and are either straight or branched chains, and the aryl portions contain from about 4 to about 16 carbons;
• or,
• (ii) R.sup.1 and R.sup.2 together form --(CH.sub.2).sub.n, where n is 1 to 4;
• or,
• (iii) R.sup.1 and R.sup.2 together form --CH.dbd.CH--;
• Ar.sup.2 is a group of formula:
• ##STR9## ps in which (i) R.sup.12 and R.sup.13 are independently selected from the group consisting of H, OH NH S, NH.sub.2, NO.sub.2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, dialkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, carbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms, preferably from 1 to 6 atoms, and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, preferably 4 to 10 carbons;
• or
• (ii) R.sup.12 and R.sup.13 together are O, S, or NR.sup.14 in which R.sup.14 is H or alkyl;
• and
• each 6-membered ring of Ar.sup.2 in formula II is unsubstituted or substituted with one to six substituents that are each independently selected from R.sup.12 or R.sup.13, as defined in (i).