Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors

被引：49

作者：

Ivanenkov, Yan A. ^{[1
,2
,3
]}

Vasilevski, Sergei V. ^{[3
]}

Beloglazkina, Elena K. ^{[3
,5
]}

Kukushkin, Maksim E. ^{[3
]}

Machulkin, Alexey E. ^{[3
,5
]}

Veselov, Mark S. ^{[2
]}

Chufarova, Nina V. ^{[2
,8
]}

Chernyaginab, Elizaveta S. ^{[2
]}

Vanzcool, Anton S. ^{[1
]}

Zyk, Nikolay V. ^{[3
]}

Skvortsov, Dmitry A. ^{[3
]}

Khutornenko, Anastasia A. ^{[4
]}

Rusanov, Alexander L. ^{[5
]}

Tonevitsky, Alexander G. ^{[6
,7
]}

Dontsova, Olga A. ^{[3
,4
]}

Majouga, Alexander G. ^{[3
,8
]}

机构：

[1] ChemDiv Inc, San Diego, CA 92121 USA

[2] Moscow Inst Phys & Technol, Dolgoprudnyi, Moskovskaya Obl, Russia

[3] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia

[4] Moscow MV Lomonosov State Univ, Belozersky Inst, Moscow 119992, Russia

[5] Moscow State Univ Mech Engn MAMI, Moscow, Russia

[6] SRC Bioclinicum, Moscow 115088, Russia

[7] PA Hertsen Moscow Res Oncol Inst, Moscow 125284, Russia

[8] Natl Univ Sci & Technol MISiS, Moscow 119049, Russia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 02期

关键词：

MDM2/p53; PPI inhibitors; Dispiro-indolinones; 3D molecular docking; Cell-based assay; FACILE SYNTHESIS; P53; CANCER; ISORHYNCHOPHYLLINE; DEGRADATION; DERIVATIVES; ACTIVATION; AUTOPHAGY; PROMOTES; TUMORS;

D O I：

10.1016/j.bmcl.2014.09.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Regioselective synthesis, biological evaluation and 3D-molecular modeling for a series of novel diastereomeric 2-thioxo-5H-dispiro[imidazolidine-4,3-pyrrolidine-2,3-indole]-2,5(1H)-diones are described. The studied compounds have been tentatively identified as potent small molecule MDM2/p53 PPI inhibitors and can therefore be reasonably regarded as promising anticancer therapeutics. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：404 / 409

页数：6

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