Patent EA-003587-B1 (EA)
Title: Method of preventing and/or treating heart failure and dysfunction with endothelin antagonists
Inventor: LYNCH JOSEPH J
IPC: A61K31/495
Filed: 1997-03-19
Abstract: 1. A method of preventing and/or treating heart failure and ventricular dysfunction in a warm blooded animal comprising to the warm blooded animal in need of such treatment a therapeutically effective amount of an endothelinant agonist of the formula: or pharmaceutically acceptable salt thereof wherein: A is a pyridinyl, substituted with C1-C6alkyl or C1-C6alkylamino. Ar<1> is - dihydrobenzofuranyl or nenzodioxolanyl, Ar<2> phenyl, substituted with methoxy- and C1-C6alkyl, substituted with C1-C6alkoxy, hydroxy-, and carboxy groups. R<1>, R<2>, and R<3> hydrogene, Y is COOH. 2. The method of Claim 1 characterized in that an endothelin antagonist selected from the group consisting of: (5R, 6S, 7S)-2-butyl-6-carboxy-7-[(R)-2-(2-carboxypropyl)-4-methoxyphneyl]-5-(3,4-methylenedioxy-phenyl)cyclopenteno[1,2-b]pyridine, (5R, 6S, 7S)-2-butyl-6-carboxy-7-[(S)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine, (5S, 6R, 7R)-2-butyl-6-carboxy-7-[(R)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine, (5S, 6R, 7R)-2-butyl-6-carboxy-7-[(S)-2-(2-carboxypropyl)-4-methoxyphenyl-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]-pyridine, (5R, 6S, 7S)-2-isopropylamino-6-carboxy-7-[(R)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine, (5R, 6S, 7S)-2-isopropylamino-6-carboxy-7-[(S)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine, (5S, 6R, 7R)-2-isopropylamino-6-carboxy-7-[(R)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxy-phenyl)cyclopenteno[1,2-b]pyridine or (5S, 6R, 7R)-2-isopropylamino-6-carboxy-7-[(S)-2-(2-carboxy-propyl)-4-methoxyphenyl)-5-(3,4-methylenedioxyphenyl)cyclopenteno[1-2-b]pyridine. (5R, 6S, 7S)-2-butyl-6-carboxy-7-[(R)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine; (5R, 6S, 7S)-2-butyl-6-carboxy-7-[(S)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine; (5S, 6R, 7R)-2-butyl-6-carboxy-7-[(R)-2-(2-carboxypropy1)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine; and (5S, 6R, 7R)-2-butyl-6-carboxy-7-[(S)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine. 3. A method of preventing and/or treating heart failure and ventricular dysfunction in a warm blooded animal which comprises administering to the warm blooded animal in need of such treatment a therapeutically effective amount of an endothelin antagonist selected from the group consisting of: (5R, 6S, 7S)-2-butyl-6-carboxy-7-[(R)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine; (5R, 6S, 7S)-2-butyl-6-carboxy-7-[(S)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine; (5S, 6R, 7R)-2-butyl-6-carboxy-7-[(R)-2-(2-carboxypropy1)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine; and (5S, 6R, 7R)-2-butyl-6-carboxy-7-[(S)-2-(2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine. 4. The method of Claim 3 wherein the heart failure is congestive heart failure. 5. The method of Claim 4 wherein the animal is a mammal. 6. The method of Claim 5 wherein the animal is human. 7. The method of Claim 1 wherein the heart failure is congestive heart failure. 8. The method of Claim 7 wherein the animal is a mammal. 9. The method of Claim 8 wherein the animal is human.