Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 1.
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). We have successfully developed novel PPPA derivatives with a 7-O-substituted benzoyl substituent that significantly exhibit more potent ACAT2 inhibitory activity and higher ACAT2 isozyme selectivity than 1.
Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Masaki
M
Ohtawa
Hiroyuki
H
Yamazaki
Satoshi
S
Ohte
Daisuke
D
Matsuda
Taichi
T
Ohshiro
Lawrence L
LL
Rudel
Satoshi
S
Omura
Hiroshi
H
Tomoda
Tohru
T
Nagamitsu
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; 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*; D013329:Structure-Activity Relationship; D000097587:Sterol O-Acyltransferase 2
D004791:Enzyme Inhibitors; D011725:Pyridines; D012717:Sesquiterpenes; D002785:Sterol O-Acyltransferase; D000097587:Sterol O-Acyltransferase 2; C082792:pyripyropene A