Studies on Agents with Vasodilator and β-Blocking Activities. V. Synthesis and Pharmacological Activity of the Optical Isomers of TZC-5665

Toshimi SEKI; Arihiro KANADA; Tomio NAKAO; Masahumi SHIRAIWA; Hajime ASANO; Katsuhiko MIYAZAWA; Tsutomu ISHIMORI; Nobuyoshi MINAMI; Kenyu SHIBATA; Kikuo YASUDA

doi:10.1248/cpb.46.84

Toshimi SEKI, Arihiro KANADA, Tomio NAKAO, Masahumi SHIRAIWA, Hajime ASANO, Katsuhiko MIYAZAWA, Tsutomu ISHIMORI, Nobuyoshi MINAMI, Kenyu SHIBATA, Kikuo YASUDA

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Keywords: chiral pyridazinone, enantioselective synthesis, asymmetric hydrogenation, hypotensive activity, β-blocking activity, phosphodiesterase III-inhibitory activity

JOURNAL FREE ACCESS

1998 Volume 46 Issue 1 Pages 84-96

DOI https://doi.org/10.1248/cpb.46.84

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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 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. R_A, S_B-one (1c) possessed the essential activities of TZC-5665 (1).

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