title: Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety.
abstract: Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by gamma-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition.
authors.affiliation: Research Center for Biological Function, Kitasato Institute, 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: Tian
authors.forename: H
authors.initials: H
authors.lastname: Tomoda
authors.forename: Y
authors.initials: Y
authors.lastname: Harigaya
authors.forename: S
authors.initials: S
authors.lastname: Omura
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D012717:Sesquiterpenes; C082792:pyripyropene A; D002785:Sterol O-Acyltransferase