A series of novel pyridazinone derivatives (II) having a phenoxypropanolamine moiety was synthesized. Their hypotensive and beta-blocking activities were evaluated after intravenous administration of the compounds to anesthetized rats. Among them, the 5-chloro-2-cyanophenoxy derivative (29) showed the promising dual activities and was selected for further studies.

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Studies on Agents with Vasodilator and β-Blocking Activities. Part 5. Synthesis and Pharmacological Activity of the Optical Isomers of TZC-5665.-All four optical isomers of the title compound are prepared. One key step is the enantiomeric hydrogenation of (III). Other double bond isomers as starting materials are less effective. By a combination of the enantiomeric catalyst and/or (R)-(VIII), whose preparation is described, the other isomers of (X) are obtained. Compound (X) possesses the essential activities of TZC-5665.-(SEKI, T.; KANADA, A.; NAKAO, T.; SHIRAIWA, M.; ASANO, H.; MIYAZAWA, K.; ISHIMORI, T.; MINAMI, N.; SHIBATA, K.; YASUDA, K.; Chem.

While treatment of the acetate (Ia) with (II) results in the formation of the reduced product (III), the analogous reaction of (Ib) or (Ic) with 3 equiv. of the higher‐order cuprate (IVa) provides the desired alkylated compound (V).