N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin

A compound of formula I:

• ##STR9## or a pharmaceutically acceptable salt of a compound of formula I, wherein:
• R.sup.1 is halide;
• R.sup.2 is selected from the group consisting of H, NH.sub.2, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, hydroxyl, 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 or cyclic, and the aryl portions contain from about 3 to about 16 carbons;
• and
• Ar.sup.2 is selected from the group consisting of:
• ##STR10## in which R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are either (i), (ii), (iii) or (iv):
• HERE
• (i) R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are each selected independently from the group consisting of H, NHOH, NH.sub.2, NO.sub.2, N.sub.3, aminoalkyl, alkylamino, dialkylamino, dialkylaminoalkyl, carboxyl, carbonyl, hydroxyl, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyalkoxy, alkylsulfinyl, alkylsulfonyl, aryloxy, arylalkoxy, aryloxy, arylamino, arylthio, arylsulfinyl, arylsulfonyl, haloalkyl, haloaryl, haloalkoxy, alkoxycarbonyl, alkylcarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido in which the alkyl, alkenyl, alkynyl portions are straight or branched chains of from 1 up to 10 carbons and the aryl portions contain from 3 to 10 carbons, and R.sup.3 is selected from the group consisting of H, carboxyl, carbonyl, hydroxyl, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyalkoxy, alkylsulfinyl, alkylsulfonyl, aryloxy, arylalkoxy, aryloxy, arylamino, arylthio, arylsulfinyl, arylsulfonyl, haloalkyl, haloaryl, haloalkoxy, alkoxycarbonyl, alkylcarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido in which the alkyl, alkenyl, alkynyl portions are straight or branched chains of from 1 up to 10 carbons and the aryl portions contain from 3 to 10 carbons;
• R.sup.8, R.sup.9 and R.sup.10 are each independently selected from H, NH.sub.2, NO.sub.2 and halide;
• X is O, S or NR.sup.11 in which R.sup.11 is H, alkyl, alkylcarbonyl or formyl;
• and n is from 0 up to about 6;
• or, alternatively,
• (ii) R.sup.4 and R.sup.7 together are substituted or unsubstituted 1, 3-butadienyl, 4-dimethylamino-1,3 butadiene, 1-chloro-1,3-butadiene, 4-diemthylamino-1,3-butadienyl, 1-aza-1,3-butadienyl or 2-aza-1,3-butadienyl groups;
• and n, X, R.sup.3, R.sup.5, R.sup.6, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are as defined in (i) above;
• or alternatively,
• (iii) R.sup.7 and R.sup.3 together are substituted or unsubstituted 1, 3-butadienyl, 4-dimethylamino-1,3 butadiene, 1-chloro-1,3-butadiene, 4-diemthylamino-1,3-butadienyl, 1-aza-1,3-butadienyl or 2-aza-1,3-butadienyl groups;
• and n, X, R.sup.4, R.sup.5, R.sup.6, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are as defined in (i);
• or alternatively
• (iv) R.sup.3, R.sup.5, and R.sup.7 are H;
• and R.sup.4 and R.sup.6 are each independently selected from the group consisting of alkyl, alkoxy, halide, amino alkyl and dialkylaminoalkyl in which the alkyl and alkoxy groups contain from 1 to 10 carbons, and are straight or branched chains;
• and R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are as defined in (i).