Format

Send to

Choose Destination
J Med Chem. 1994 Jun 24;37(13):2079-84.

Novel acyl-CoA:cholesterol acyltransferase inhibitors. Synthesis and biological activity of 3-quinolylurea derivatives.

Author information

1
Pharmaceutical Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan.

Abstract

A series of 3-quinolylurea derivatives (1) was synthesized and evaluated for acyl-CoA:cholesterol acyltransferase (ACAT) inhibitory activity. For in vitro studies, the most potent inhibitory activity was found in derivatives having substituents at the 6,7- or 6,8-positions and an ortho-substituted phenyl group at the 4-position of quinoline ring. The 2,4-difluorophenyl group appeared to be the optimum N'-substituent of the urea moiety. The IC50 values of compounds 52-54 and 59 were in the nanomolar order. Plasma cholesterol-lowering activity of compounds 50, 52, and 54 was observed at less than 1 mg/kg/day in cholesterol-fed rats. Compound 52 was also hypocholesterolemic in hamsters fed a diet without loading cholesterol.

PMID:
8027989
DOI:
10.1021/jm00039a020
[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center