title: Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 3.
abstract: In an effort to develop potent and selective inhibitors toward ACAT2, structure-activity relationship studies were carried out using derivatives based on pyripyropene A (PPPA, 1). In particular, we investigated the possibility of introducing appropriate 1,11-O-benzylidene and 7-O-substituted benzoyl moieties into PPPA (1). The new o-substituted benzylidene derivatives showed higher selectivity for ACAT2 than PPPA (1). Among them, 1,11-O-o-methylbenzylidene-7-O-p-cyanobenzoyl PPPA derivative 7q and 1,11-O-o,o-dimethylbenzylidene-7-O-p-cyanobenzoyl PPPA derivative 7z proved to be potent ACAT2 inhibitors with unprecedented high isozyme selectivity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Tokyo 108-8641, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohtawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohte
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuda
authors.forename: Taichi
authors.initials: T
authors.lastname: Ohshiro
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Rudel
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.forename: Tohru
authors.initials: T
authors.lastname: Nagamitsu
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000097587:Sterol O-Acyltransferase 2
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D012717:Sesquiterpenes; D002785:Sterol O-Acyltransferase; D000097587:Sterol O-Acyltransferase 2; C082792:pyripyropene A