Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B

Wen-Wei Qiu; Qiang Shen; Fan Yang; Bo Wang; Hui Zou; Jing-Ya Li; Jia Li; Jie Tang

doi:10.1016/j.bmcl.2009.10.017

Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6618-22. doi: 10.1016/j.bmcl.2009.10.017. Epub 2009 Oct 8.

Authors

Wen-Wei Qiu¹, Qiang Shen, Fan Yang, Bo Wang, Hui Zou, Jing-Ya Li, Jia Li, Jie Tang

Affiliation

¹ Institute of Medicinal Chemistry, Department of Chemistry, East China Normal University, Shanghai 200062, China.

PMID: 19846303
DOI: 10.1016/j.bmcl.2009.10.017

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Molecular Conformation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship
Triterpenes / chemical synthesis*
Triterpenes / chemistry
Triterpenes / pharmacology*

Substances

Enzyme Inhibitors
Triterpenes
maslinic acid
Protein Tyrosine Phosphatase, Non-Receptor Type 1