Journal of Medicinal Chemistry p. 1067 - 1083 (1995)
Update date:2022-07-29
Topics:
Maduskuie, Thomas P.
Wilde, Richard G.
Billheimer, Jeffrey T.
Cromley, Debra A.
Germain, Sandra
et al.
Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification.Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the development of fatty streaks.Inhibitors of the ACAT enzyme may retard this atherogenic process.We have recently discovered a series of imidazoles which are potent in vitro ACAT inhibitors in the J774 macrophage cell culture assay.This paper will describe the design, synthesis, and structure-activity relationship for this very potent series of compounds.
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