Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B.
A series of maslinic acid derivatives have been synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Most of the compounds exhibited a dramatic increase in inhibitory potency and selectivity, the two most potent PTP1B inhibitors 20 (IC(50)=0.61 microM) and 29 (IC(50)=0.64 microM) showed about 10-fold more potent than lead compound maslinic acid. More importantly, 29 possesses the best selectivity of 6.9-fold for PTP1B over TCPTP.
Institute of Medicinal Chemistry, Department of Chemistry, East China Normal University, Shanghai 200062, China.
Wen-Wei
WW
Qiu
Qiang
Q
Shen
Fan
F
Yang
Bo
B
Wang
Hui
H
Zou
Jing-Ya
JY
Li
Jia
J
Li
Jie
J
Tang
D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
D004791:Enzyme Inhibitors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid