Studies on Agents with Vasodilator and β-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 reaction of chiral diaminopyridazinone (2) with chiral glycidyl ether (3). The hypotensive and β-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).