Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-Cyclic analogs.
A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is benzylidene acetal analog 35, the most potent inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16 times more potent inhibitory activity than pyripyropene A.
Obata
R
R
Research Center for Biological Function, Kitasato Institute, Kitasato University, Tokyo, Japan.
Sunazuka
T
T
Kato
Y
Y
Tomoda
H
H
Harigaya
Y
Y
Omura
S
S
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011725:Pyridines; D011753:Pyrones; D012717:Sesquiterpenes; C082792:pyripyropene A; D002785:Sterol O-Acyltransferase