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

doi:10.3987/COM-94-6720

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

Molecular Genetics

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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 language	English (US)
Pages (from-to)	1551-1571
Number of pages	21
Journal	Heterocycles
Volume	38
Issue number	7
DOIs	https://doi.org/10.3987/COM-94-6720
State	Published - Jul 1 1994

ASJC Scopus subject areas

Analytical Chemistry
Pharmacology
Organic Chemistry

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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, 38(7), 1551-1571. https://doi.org/10.3987/COM-94-6720

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. https://doi.org/10.3987/COM-94-6720

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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.",

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

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AU - Kanaya, Naoaki

AU - Nagashima, Hajime

AU - Usui, Hiroyuki

AU - Oshima, Reiko

AU - Kanao, Munefumi

AU - Tomoda, Hiroshi

AU - Sunazuka, Toshiaki

AU - Nagamitsu, Tohru

AU - Kumagai, Hidetoshi

AU - Omura, Satoshi

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

Abstract

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