Dihydropyrimidines: Novel Calcium Antagonists with Potent and Long-Lasting Vasodilative and Antihypertensive Activity

Hidetsura Cho, Masaru Ueda, Keivuu Shima, Akira Mizuno, Mariko Havashimatsu, Yoshiko Ohnaka, Yumi Takeuchi, Mikiko Hamaguchi, Kazuo Aisaka, Toshinori Hidaka, Masanori Kawai, Minako Takeda, Takafumi Ishihara, Kazuteru Funahashi, Fumio Satoh, Minoru Morita, Teruhisa Noguchi

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

The novel calcium antagonists 3-N-substituted-3,4-dihydropyrimidines 1 and 9 and 3-N-substituted-dihydro-pyrimidin-2(lH)-ones 8 were regioselectively synthesized in good yields. Compounds 1 [especially 1s [R1= (CH2)2 N(benzyl)(2-naphthylmethyl), R2= i-Pr, X = o-NO2] and It [R1= (CH2)2 N(benzyl)(3,4-dichlorobenzyl), R2= i-Pr, X = o-n O2]] exhibited not only more potent and longer lasting vasodilative action but also a hypotensive activity with slow onset as compared with dihydropyridines. Moreover, some dihydropyrimidines [lq [R1= (CH2)2 N(benzyl)(3-phenylpropyl), R2= CH2(cyclopropyl), X = o-NO2], Is, and It] were weaker in blocking atrioventricular conduction in anesthetized open-chest dogs and less toxic than the dihydropyridines.

Original languageEnglish
Pages (from-to)2399-2406
Number of pages8
JournalJournal of Medicinal Chemistry
Volume32
Issue number10
DOIs
Publication statusPublished - 1989 Oct 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Cho, H., Ueda, M., Shima, K., Mizuno, A., Havashimatsu, M., Ohnaka, Y., Takeuchi, Y., Hamaguchi, M., Aisaka, K., Hidaka, T., Kawai, M., Takeda, M., Ishihara, T., Funahashi, K., Satoh, F., Morita, M., & Noguchi, T. (1989). Dihydropyrimidines: Novel Calcium Antagonists with Potent and Long-Lasting Vasodilative and Antihypertensive Activity. Journal of Medicinal Chemistry, 32(10), 2399-2406. https://doi.org/10.1021/jm00130a029