Synthesis and biological evaluation of novel pyrazolo[4,3-b]oleanane derivatives as inhibitors of glycogen phosphorylase

Eighteen pyrazolo4,3-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 pyrazolo4,3-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 pyrazolo4,3-b]oleanane derivatives as GPa inhibitors is discussed.