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

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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-1-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)513-520
Number of pages8
JournalChemical and Pharmaceutical Bulletin
Volume42
Issue number3
StatePublished - 1994

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antibiotic 1233A
Hydroxymethylglutaryl-CoA Synthase
Propiolactone
Bioactivity
Structure-Activity Relationship
Conformations

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

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

In: Chemical and Pharmaceutical Bulletin, Vol. 42, No. 3, 1994, p. 513-520.

Research output: Contribution to journalArticle

Hashizume, H. ; Ito, H. ; Yamada, K. ; Nagashima, H. ; Kanao, M. ; Tomoda, H. ; Sunazuka, T. ; Kumagai, H. ; Omura, S. / 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. In: Chemical and Pharmaceutical Bulletin. 1994 ; Vol. 42, No. 3. pp. 513-520.
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AU - Tomoda, H.

AU - Sunazuka, T.

AU - Kumagai, H.

AU - Omura, S.

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