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, Kitasato University, Tokyo, Japan.
authors.initials: R
authors.lastname: Obata
authors.initials: T
authors.lastname: Sunazuka
authors.initials: Z
authors.lastname: Tian
authors.initials: H
authors.lastname: Tomoda
authors.initials: Y
authors.lastname: Harigaya
authors.initials: S
authors.lastname: Omura