SYNTHESIS AND BIOLOGICAL-ACTIVITY OF NEW 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE INHIBITORS - 2-OXETANONES WITH A META-SUBSTITUENT ON THE BENZENE-RING IN THE SIDE-CHAIN

被引：0

作者：

HASHIZUME, H

ITO, H

KANAYA, N

NAGASHIMA, H

USUI, H

OSHIMA, R

KANAO, M

TOMODA, H

SUNAZUKA, T

KUMAGAI, H

OMURA, S

机构：

[1] DAIICHI PHARMACEUT CO LTD, EDOGAWA KU, TOKYO 134, JAPAN

[2] KITASATO INST, BIOL FUNCT RES CTR, MINATO KU, TOKYO 108, JAPAN

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 1994年 / 42卷 / 06期

关键词：

3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE; INHIBITOR; CHOLESTEROL BIOSYNTHESIS; 2-OXETANONE; 1233A ANALOG; STRUCTURE-ACTIVITY RELATIONSHIP;

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Isosteric side chain analogs of 3a were synthesized and tested for inhibitory activities towards 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and upon cholesterol production in Hep G2 cells and in mouse liver. It became clear that the lipophilic substituent on the aromatic ring and the terminal hydrophilic group in the side chain were important in the enhancement of activity. 4-[2-(3-n-Hexyloxyphenyl)ethyl]-3-hydroxy-methyl-2-oxetanone (5a) showed equivalent inhibitory activity in vivo to that of 1233A.

引用

页码：1272 / 1278

页数：7

共 8 条

[1]

CORE YEJ, 1961, J AM CHEM SOC, V91, P5675

[2] INHIBITION OF CHOLESTEROL-SYNTHESIS INVITRO AND INVIVO BY ML-236A AND ML-236B, COMPETITIVE INHIBITORS OF 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE [J].