Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction

被引：96

作者：

Hardcastle, IR

Ahmed, SU

Atkins, H

Calvert, AH

Curtin, NJ

Farnie, G

Golding, BT

Griffin, RJ

Guyenne, S

Hutton, C

Källbad, P

Kemp, SJ

Kitching, MS

Newell, DR

Norbedo, S

Northen, JS

Reid, RJ

Saravanan, K

Willems, HMG

Lunec, J

机构：

[1] Univ Newcastle Upon Tyne, Sch Nat Sci Chem, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[2] Univ Newcastle Upon Tyne, Sch Med, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[3] De Novo Pharmaceut, Cambridge CB4 9ZR, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 05期

基金：

英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

cancer; MDM2; p53; protein-protein interactions;

D O I：

10.1016/j.bmcl.2004.12.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-N-alkyl-3-aryl-3-alkoxyisoindolinones has been synthesised and evaluated as inhibitors of the MDM2-p53 interaction. The most potent compound, 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1-one (NU8231), exhibited an IC50 of 5.3 +/- 0.9 mu M in an ELISA assay, and induced p53-dependent gene transcription in a dose-dependent manner, in the SJSA human sarcoma cell line. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1515 / 1520

页数：6

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