Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases

被引：50

作者：

Nishiguchi, Gisele A. ^{[1
]}

Atallah, Gordana ^{[1
]}

Bellamacina, Cornelia ^{[1
]}

Burger, Matthew T. ^{[1
]}

Ding, Yu ^{[1
]}

Feucht, Paul H. ^{[2
]}

Garcia, Pablo D. ^{[2
]}

Han, Wooseok ^{[1
]}

Klivansky, Liana ^{[1
,2
,3
]}

Lindvall, Mika ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, Global Discovery Chem Oncol & Exploratory Chem, Emeryville, CA 94608 USA

[2] Novartis Inst BioMed Res, Oncol Res, Emeryville, CA 94608 USA

[3] Univ Calif Berkeley, Lawrence Berkeley Lab, Mol Foundry, Berkeley, CA 94720 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 21期

关键词：

Pim-kinase inhibitors; Indole; Kinase selectivity; Oncology; PROTOONCOGENE PIM-1; BINDING MODE; CELL; CANCER; PROGRESSION; TUMORIGENESIS; EXPRESSION; APOPTOSIS; LYMPHOMA; SURVIVAL;

D O I：

10.1016/j.bmcl.2011.08.105

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 3,5-disubstituted indole derivatives as potent and selective inhibitors of all three members of the Pim kinase family is described. High throughput screen identified a pan-Pim kinase inhibitor with a promiscuous scaffold. Guided by structure-based drug design, SAR of the series afforded a highly selective indole chemotype that was further developed into a potent set of compounds against Pim-1, 2, and 3 (Pim-1 and Pim-3: IC(50) <= 2 nM and Pim-2: IC(50) <= 100 nM). (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：6366 / 6369

页数：4

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