Synthesis and biological evaluation of novel pyrazolo[4,3-b]oleanane derivatives as inhibitors of glycogen phosphorylase.
Eighteen pyrazolo[4,3-b]oleanane derivatives have been synthesized and biologically evaluated as inhibitors of rabbit muscle GPa. Key compound 5 was readily obtained in four steps starting from oleanolic acid (OA; 1). Further modification based on pyrazolo triterpene 5 resulted in 17 novel pyrazolo pentacyclic triterpenes. All of the synthesized pyrazolo[4,3-b]oleanane derivatives were biologically assayed against rabbit muscle GPa. Within this series of compounds, pyrazole triterpene 19 (IC(50)=9.9 microM) exhibited more potent activity than the parent compound 1. Preliminary structure-activity relationship analysis of the pyrazolo[4,3-b]oleanane derivatives as GPa inhibitors is discussed.
Chen
Jun
J
Center for Drug Discovery, School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, P. R. China.
Gong
Yanchun
Y
Liu
Jun
J
Hua
Weiyi
W
Zhang
Luyong
L
Sun
Hongbin
H
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D009132:Muscles / Q000201:enzymology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D009828:Oleanolic Acid; D024981:Glycogen Phosphorylase