title: Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups.
abstract: Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity (IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).
authors.affiliation: Research Center for Biological Function, Kitasato Institute, Kitasato University, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Obata
authors.forename: T
authors.initials: T
authors.lastname: Sunazuka
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Tian
authors.forename: Y
authors.initials: Y
authors.lastname: Harigaya
authors.forename: N
authors.initials: N
authors.lastname: Tabata
authors.forename: H
authors.initials: H
authors.lastname: Tomoda
authors.forename: S
authors.initials: S
authors.lastname: Omura
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000493:pharmacokinetics; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology*; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D011753:Pyrones; D002784:Cholesterol; D002785:Sterol O-Acyltransferase