Abstract: Compounds of formula (I) and pharmaceutical compositions containing the compounds of formula (I): ##STR1## are provided. In formula (I): Ar is a substituted or unsubstituted aromatic or heterocyclic group; R is H or a substituted or unsubstituted straight or branched chain, cyclic or mixture of straight branched and cyclic alkyl, alkenyl, or alkynyl group having from 1-20 carbon atom; A is a functional group that bears a polar moiety; R.sub.1 is R, R--C=0, R substituted with one or more heteroatoms, a substituted or unsubstituted aryl group, or is aryl-(CH.sub.2).sub.n ; R.sub.2 is (CH.sub.2).sub.n, CHR, C(R).sub.2, COO, OCO, NHCO, CONH, SO, SO.sub.2 or NR; R.sub.3 and R.sub.4, which are the same or different or each may be absent, and are .dbd.O, H, O-aryl, OR, O-alkyl or alkyl, aryl, SR, S-aryl, NHR, NH-aryl, NR, or are other heteroaromatic groups; R.sub.5 is H, OH or R; E and F, which are the same or are different, are either N or (CH.sub.2).sub.

Abstract: N-(4-halo-isoxazolyl)sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(4-halo-3-isoxazolyl)sulfonamides and N-(4-halo-5-isoxazolyl)benzenesulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: N-(5-isoxazolyl)biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.