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

doi:10.1248/cpb.42.512

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

Molecular Genetics

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

17 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 language	English (US)
Pages (from-to)	512-520
Number of pages	9
Journal	Chemical and Pharmaceutical Bulletin
Volume	42
Issue number	3
DOIs	https://doi.org/10.1248/cpb.42.512
State	Published - 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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Hashizume, H., Ito, H., Yamada, K., Nagashima, H., Kanao, M., Tomoda, H., Sunazuka, T., Kumagai, H., & Omura, S. (1994). 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. Chemical and Pharmaceutical Bulletin, 42(3), 512-520. https://doi.org/10.1248/cpb.42.512

Hashizume, H, Ito, H, Yamada, K, Nagashima, H, Kanao, M, Tomoda, H, Sunazuka, T, Kumagai, H & Omura, S 1994, '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', Chemical and Pharmaceutical Bulletin, vol. 42, no. 3, pp. 512-520. https://doi.org/10.1248/cpb.42.512

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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-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.",

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

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AU - Hashizume, H.

AU - Ito, H.

AU - Yamada, K.

AU - Nagashima, H.

AU - Kanao, M.

AU - Tomoda, H.

AU - Sunazuka, T.

AU - Kumagai, H.

AU - Omura, S.

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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

Abstract

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