STUDIES ON AGENTS WITH VASODILATOR AND BETA-BLOCKING ACTIVITIES - V -SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF THE OPTICAL ISOMERS OF TZC-5665

Synthesis of the four optical isomers of TZC-5665 (1), a candidate for the treatment of congestive heart failure, was achieved by the reacti on of chiral diaminopyridazinone (2) with chiral glycidyl ether (3). T he hypotensive and beta-blocking activities of 1 and its optical isome rs were examined when given intravenously into anesthetized rats. Furt hermore these compounds were evaluated for inhibitory activity on cAMP phosphodiesterase III. Among the four optical isomers, R-A,S-B-one (1 c) possessed the essential activities of TZC-5665 (1).