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
Alonso, A
Sasin, J
Bottini, N
Friedberg, I
Friedberg, I
Osterman, A
Godzik, A
Hunter, T
Dixon, J
Mustelin, T
[J]. CELL, 2004, 117 (06) : 699 - 711
[2] Genetic analysis of the kinome and phosphatome in cancer
Arena, S
Benvenuti, S
Bardelli, A
[J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2005, 62 (18) : 2092 - 2099
[3] Dissociation of PTPase levels from their modulation of insulin receptor signal transduction
Bleyle, LA
Peng, Y
Ellis, C
Mooney, RA
[J]. CELLULAR SIGNALLING, 1999, 11 (10) : 719 - 725
[4] Antimicrobial triterpenoids from Licania heteromorpha
Braca, A
Morelli, I
Mendez, J
Battinelli, L
Braghiroli, L
Mazzanti, G
[J]. PLANTA MEDICA, 2000, 66 (08) : 768 - 769
[5] Divalent and trivalent α-ketocarboxylic acids as inhibitors of protein tyrosine phosphatases
Chen, YT
Seto, CT
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (18) : 3946 - 3952
[6] Coordinated action of protein tyrosine phosphatases in insulin signal transduction
Cheng, A
Dubé, N
Gu, F
Tremblay, ML
[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 2002, 269 (04): : 1050 - 1059
[7] Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B
Cheng, A
Uetani, N
Simoncic, PD
Chaubey, VP
Lee-Loy, A
McGlade, CJ
Kennedy, BP
Tremblay, ML
[J]. DEVELOPMENTAL CELL, 2002, 2 (04) : 497 - 503
[8] Enantiopure N-protected α-amino glyoxals 1.: Synthesis from α-amino acids and some condensation reactions with amines
Darkins, P
Groarke, M
McKervey, MA
Moncrieff, HM
McCarthy, N
Nieuwenhuyzen, M
[J]. JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 2000, (03): : 381 - 389
[9] HALOGENOLYSIS OF METHYL GLYCYRRHETATE WITH LITHIUM IODIDE-DIMETHYLFORMAMIDE
DEAN, PDG
[J]. JOURNAL OF THE CHEMICAL SOCIETY, 1965, (NOV): : 6655 - &
[10] Linear versus angular Fischer indole annulation: Relative configuration determines regioselectivity
Diedrich, Claas Lueder
Frey, Wolfgang
Christoffers, Jens
[J]. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2007, 2007 (28) : 4731 - 4737

← 1 2 3 4 5 →