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Acyl CoA:cholesterol acyltransferase (ACAT) inhibitors: synthesis and structure-activity relationship studies of a new series of trisubstituted imidazoles.

Abstract：

:A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles has been synthesized and demonstrated to be potent inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). The design, synthesis, and structure-activity relationships for this series are reported herein. One of the compounds from this series, N'-(2,4-difluorophenyl)-N-[5-[(4,5-diaryl-1H-imidazol-2- yl)thio]pentyl]-N-heptylurea (DuP 128), was selected for development as an intestinally active ACAT inhibitor. DuP 128 is a potent ACAT inhibitor in vitro and in vivo, inhibiting ACAT in rat hepatic microsomes with an IC50 = 10 nM and possessing potent antihypercholesterolemic activity in vivo.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Higley CA,Wilde RG,Maduskuie TP,Johnson AL,Pennev P,Billheimer JT,Robinson CS,Gillies PJ,Wexler RR

doi

10.1021/jm00047a009

subject

Has Abstract

pub_date

1994-10-14 00:00:00

pages

3511-22

issue

21

eissn

0022-2623

issn

1520-4804

journal_volume

37

pub_type

杂志文章

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