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

被引：64

作者：

Qiu, Wen-Wei ^{[2
]}

Shen, Qiang ^{[1
]}

Yang, Fan ^{[2
]}

Wang, Bo ^{[2
]}

Zou, Hui ^{[2
]}

Li, Jing-Ya ^{[1
]}

Li, Jia ^{[1
]}

Tang, Jie ^{[2
]}

机构：

[1] Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China

[2] E China Normal Univ, Inst Med Chem, Dept Chem, Shanghai 200062, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 23期

基金：

中国国家自然科学基金;

关键词：

Maslinic acid; Protein tyrosine phosphatase 1B; Inhibitor; SAR; Diabetes; OCCURRING PENTACYCLIC TRITERPENES; SIDE-CHAIN MIMETICS; COLON-CANCER CELLS; INSULIN-RECEPTOR; SIGNAL-TRANSDUCTION; GLYCOGEN-PHOSPHORYLASE; NATURAL-PRODUCTS; APOPTOSIS; MICE; MACROPHAGES;

D O I：

10.1016/j.bmcl.2009.10.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (IC50 = 0.61 mu M) and 29 (IC50 = 0.64 mu M) 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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6618 / 6622

页数：5

共 45 条

[1] Protein tyrosine phosphatases in the human genome [J].