Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase.
The 3-deoxy-2-keto derivatives 5 and 7 of oleanolic acid (1) and ursolic acid (2), respectively, served as precursors to the synthesis of 35 3-deoxy derivatives of pentacyclic triterpenes. The synthesized compounds were biologically assayed for their inhibitory activity against rabbit muscle glycogen phosphorylase a (GPa). Among this series of compounds, 2alpha-hydroxyurs-12-en-28-oic acid (18) (IC(50) = 1.2 microM) exhibited the most potent activity. Preliminary structure-activity relationship analysis for the 3-deoxy triterpene derivatives as GP inhibitors is also discussed.
Zhang
Pu
P
Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, People's Republic of China.
Hao
Jia
J
Liu
Jun
J
Lu
Qian
Q
Sheng
Huaming
H
Zhang
Luyong
L
Sun
Hongbin
H
D000818:Animals; D015195:Drug Design; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009828:Oleanolic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053978:Pentacyclic Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000097245:Ursolic Acid
D024981:Glycogen Phosphorylase; D009828:Oleanolic Acid; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000097245:Ursolic Acid; C113861:corosolic acid