3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITORS .6. TRANS-6-[2-(SUBSTITUTED-1-NAPHTHYL)ETHYL(OR -ETHENYL)]-3,4,5,6-TETRAHYDRO-4-HYDROXY-2H-PYRAN-2-ONES

被引：46

作者：

PRUGH, JD ^{[1
]}

ALBERTS, AW ^{[1
]}

DEANA, AA ^{[1
]}

GILFILLIAN, JL ^{[1
]}

HUFF, JW ^{[1
]}

SMITH, RL ^{[1
]}

WIGGINS, JM ^{[1
]}

机构：

[1] MERCK SHARP & DOHME LTD,RAHWAY,NJ 07065

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 02期

关键词：

D O I：

10.1021/jm00164a047

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A variety of trans-6-[2-(aubstituted-1-naphthyl)ethyl(or ethenyl)]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones were prepared and, upon conversion to their 3,5-dihydroxy carboxylates, were found to have good inhibitory activity against the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-determining enzyme in cholest-erogenesis. The most active compounds are 2,4,6- and 2,4,7-trichloro derivatives and would be expected to display about the same potency as the standard compactin (la) upon resolution. © 1990, American Chemical Society. All rights reserved.

引用

页码：758 / 765

页数：8

共 21 条

[1] IRREVERSIBLE ENZYME INHIBITORS .160. SOME FACTORS IN CELL WALL TRANSPORT OF ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF DIHYDROFOLIC REDUCTASE DERIVED FROM 4,6-DIAMINO-1,2-DIHYDRO-2,2-DIMETHYL-L-(PHENYLALKYLPHENYL)-S-TRIAZINES [J].