Synthesis and Biological Activity of New 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Synthase Inhibitors: 2-Oxetanones with a Side Chain Mimicking the Folded Structure of 1233A

H. Hashizume, H. Ito, K. Yamada, H. Nagashima, M. Kanao, H. Tomoda, T. Sunazuka, H. Kumagai, S. Omura

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-l-naphthyl)ethyl]-2-oxetanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.

Original languageEnglish (US)
Pages (from-to)512-520
Number of pages9
JournalChemical and Pharmaceutical Bulletin
Volume42
Issue number3
DOIs
StatePublished - 1994

Keywords

  • 1233A analog
  • 2-oxetanone
  • 3-hydroxy-3-methylglutaryl coenzyme A synthase
  • cholesterol biosynthesis
  • inhibitor
  • structure-activity relationship

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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