Studies on agents with vasodilator and beta-blocking activities. V. Synthesis and pharmacological activity of the optical isomers of TZC-5665.

Abstract

Synthesis of the four optical isomers of TZC-5665 (1), a candidate for the treatment of congestive heart failure, was achieved by the reaction of chiral diaminopyridazinone (2) with chiral glycidyl ether. (3). The hypotensive and beta-blocking activities of 1 and its optical isomers were examined when given intravenously into anesthetized rats. Furthermore these compounds were evaluated for inhibitory activity on cAMP phosphodiesterase III. Among the four optical isomers, Ra,Sb-one (1c) possessed the essential activities of TZC-5665 (1).

• Authors: T Seki, A Kanada, T Nakao, M Shiraiwa, H Asano, K Miyazawa, T Ishimori, N Minami, K Shibata, K Yasuda
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 46 Issue 1 Pg. 84-96 (Jan 1998) ISSN: 0009-2363 [Print] Japan
• PMID: 9468640 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Antihypertensive Agents
• Cardiovascular Agents
• Enzyme Inhibitors
• Epoxy Compounds
• Pyridazines
• Vasodilator Agents
• glycidyl ethers
• TZC 5665
• 3',5'-Cyclic-AMP Phosphodiesterases

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors)
• Adrenergic beta-Antagonists (chemical synthesis, pharmacology)
• Animals
• Antihypertensive Agents (chemical synthesis, pharmacology)
• Cardiovascular Agents (chemical synthesis, pharmacology)
• Enzyme Inhibitors (pharmacology)
• Epoxy Compounds (chemistry)
• Heart Failure (drug therapy)
• Injections, Intravenous
• Pyridazines (chemical synthesis, pharmacology)
• Rats
• Stereoisomerism
• Structure-Activity Relationship
• Vasodilator Agents (chemical synthesis, pharmacology)