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J Med Chem. 1994 Oct 14;37(21):3511-22.

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

Author information

1
DuPont Merck Research Laboratories, Wilmington, Delaware 19880-0402.

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.

PMID:
7932580
DOI:
10.1021/jm00047a009
[Indexed for MEDLINE]

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