Synthesis and biological activities of new HMG-COA synthase inhibitors: 2-Oxetanones with a side chain containing biphenyl, terphenyl or phenylpyridine

Hirokazu Hashizume, Hajime Ito, Naoaki Kanaya, Hajime Nagashima, Hiroyuki Usui, Reiko Oshima, Munefumi Kanao, Hiroshi Tomoda, Toshiaki Sunazuka, Tohru Nagamitsu, Hidetoshi Kumagai, Satoshi Omura

Research output: Contribution to journalArticle

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Abstract

A series of 1233A analogs containing biphenylyl, terphenylyl or phenylpyridyl groups in their side chain were synthesized and tested for the inhibitory activities against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and inhibition for the cholesterol biosynthesis in the mouse liver. The compounds with an oxetane, cyclobutanone or γ -butyrolactone ring as isosters of a 2-oxetanone ring were entirely inactive. Among sythetic analogs, anti-4-[3-[2-(5-isopropyl-2-pyridyl)-ethyl]-phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (10b) was most active in vitro. The structure-activity relationships on the transformations of 2-oxetanone and its side chain were obtained.

Original languageEnglish (US)
Pages (from-to)1551-1571
Number of pages21
JournalHeterocycles
Volume38
Issue number7
StatePublished - Jul 1 1994

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Propiolactone
Bioactivity
antibiotic 1233A
Hydroxymethylglutaryl-CoA Synthase
Biosynthesis
Structure-Activity Relationship
Liver
Cholesterol
diphenyl

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Hashizume, H., Ito, H., Kanaya, N., Nagashima, H., Usui, H., Oshima, R., ... Omura, S. (1994). Synthesis and biological activities of new HMG-COA synthase inhibitors: 2-Oxetanones with a side chain containing biphenyl, terphenyl or phenylpyridine. Heterocycles, 38(7), 1551-1571.

Synthesis and biological activities of new HMG-COA synthase inhibitors : 2-Oxetanones with a side chain containing biphenyl, terphenyl or phenylpyridine. / Hashizume, Hirokazu; Ito, Hajime; Kanaya, Naoaki; Nagashima, Hajime; Usui, Hiroyuki; Oshima, Reiko; Kanao, Munefumi; Tomoda, Hiroshi; Sunazuka, Toshiaki; Nagamitsu, Tohru; Kumagai, Hidetoshi; Omura, Satoshi.

In: Heterocycles, Vol. 38, No. 7, 01.07.1994, p. 1551-1571.

Research output: Contribution to journalArticle

Hashizume, H, Ito, H, Kanaya, N, Nagashima, H, Usui, H, Oshima, R, Kanao, M, Tomoda, H, Sunazuka, T, Nagamitsu, T, Kumagai, H & Omura, S 1994, 'Synthesis and biological activities of new HMG-COA synthase inhibitors: 2-Oxetanones with a side chain containing biphenyl, terphenyl or phenylpyridine', Heterocycles, vol. 38, no. 7, pp. 1551-1571.
Hashizume, Hirokazu ; Ito, Hajime ; Kanaya, Naoaki ; Nagashima, Hajime ; Usui, Hiroyuki ; Oshima, Reiko ; Kanao, Munefumi ; Tomoda, Hiroshi ; Sunazuka, Toshiaki ; Nagamitsu, Tohru ; Kumagai, Hidetoshi ; Omura, Satoshi. / Synthesis and biological activities of new HMG-COA synthase inhibitors : 2-Oxetanones with a side chain containing biphenyl, terphenyl or phenylpyridine. In: Heterocycles. 1994 ; Vol. 38, No. 7. pp. 1551-1571.
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