Details

Autor(en) / Beteiligte

• Clader, John W
• Burnett, Duane A
• Caplen, Mary Ann
• Domalski, Martin S
• Dugar, Sundeep
• Vaccaro, Wayne
• Sher, Rosy
• Browne, Margaret E
• Zhao, Hongrong
• Burrier, Robert E
• Salisbury, Brian
• Davis, Harry R

Titel

2-Azetidinone Cholesterol Absorption Inhibitors:  Structure−Activity Relationships on the Heterocyclic Nucleus

Ist Teil von

• Journal of medicinal chemistry, 1996-09, Vol.39 (19), p.3684-3693

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1996

Quelle

MEDLINE

Beschreibungen/Notizen

• A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((−)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA:cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure−activity relationships consistent with a well-defined molecular target. The details of these structure−activity relationships and their implications on the nature of the putative pharmacophore are discussed.