Sulfonamides and derivatives thereof that modulate the activity of endothelin

SULFONAMIDS AND METHODS OF USING THESE SULFONAMIDS ARE PRESENTED TO INHIBIT THE UNION OF AN ENDOTHELINE PEPTIDE TO AN ENDOTHELINE RECEPTOR THROUGH THE RECEIVER CONTACT WITH SULFONAMIDE. METHODS ARE ALSO PRESENTED FOR THE TREATMENT OF DISEASES INTERMEDIATED BY ENDOTHELINE THROUGH THE ADMINISTRATION OF EFFECTIVE AMOUNTS OF ONE OR MORE OF THESE SULFONAMIDS OR DRUGS OF THE SAME THAT INHIBIT OR INCREASE THE ACTIVITY OF ENDOTHELINE. THE SULFONAMIDS HAVE FORMULA (I) IN WHICH AR {SUP, 1} IS 3- OR 5- ISOXAZOIL AND AR {SUP, 2} IS SELECTED BETWEEN RENT, INCLUDING ANALOGS OF THE SAME STRAIGHT AND BRANCHED CHAINS, OF AROMATIC RINGS, OF FUNDED AROMATIC RINGS AND HETEROCICLIC RINGS, INCLUDING HETEROCICLES OF 5 MEMBERS WITH 1,2 OR MORE HETEROATOMOS AND OF FUNDED RING AND ANALOGS OF THE SAME RINGS OF 6 MEMBERS WITH 1,2 OR MORE HETEROATOMS AND FUNDED RING. AR {SUP, 2} IS PREFERIBLY THIOPHENYL, FURILE, PIRROLYL, NAFTILO AND PHENYL. THE COMPOUNDS IN WHICH AR {SUP, 1} IS A 4-HALO-SUBSTITUTED ISOXAZOLA ARE MORE ACTIVE THAN THE SUBSTITUTED COMPOUNDS WITH CORRESPONDING RENT AND THE COMPOUNDS IN WHICH AR {SUP, 1} IS REPLACED IN THIS POSITION WITH A HIGHER RENT TO EXHIBIT A GREATER ACTIVITY FOR THE RECEIVERS OF THE ET {SUB, B} THAN THE SUBSTITUTED COMPOUNDS WITH CORRESPONDING LOWER RENT.