Scaffold oriented synthesis. Part 2: Design, synthesis and biological evaluation of pyrimido-diazepines as receptor tyrosine kinase inhibitors

被引：25

作者：

Gracias, Vijaya ^{[1
]}

Ji, Zhiqin ^{[1
]}

Akritopoulou-Zanze, Irini ^{[1
]}

Abad-Zapatero, Cele ^{[1
]}

Huth, Jeffrey R. ^{[1
]}

Song, Danying ^{[1
]}

Hajduk, Philip J. ^{[1
]}

Johnson, Eric F. ^{[1
]}

Glaser, Keith B. ^{[1
]}

Marcotte, Patrick A. ^{[1
]}

Pease, Lori ^{[1
]}

Soni, Nirupama B. ^{[1
]}

Stewart, Kent D. ^{[1
]}

Davidsen, Steven K. ^{[1
]}

Michaelides, Michael R. ^{[1
]}

Djuric, Stevan W. ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60044 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 08期

关键词：

KDR inhibitors; VEGFR; PDGFR; cKit inhibitors; Flt3; inhibitors; adenine mimics; structure-based drug design;

D O I：

10.1016/j.bmcl.2008.03.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the discovery of the pyrimido-diazepine scaffolds as novel adenine mimics. Structure-based design led to the discovery of analogs with potent inhibitory activity against receptor tyrosine kinases, such as KDR, Flt3 and c-Kit. Compound 14 exhibited low nanomolar KDR enzymatic and cellular potencies (IC50 = 9 and 52 nM, respectively). (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2691 / 2695

页数：5

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