Optimization of triarylimidazoles for Tie2: Influence of conformation on potency

被引：27

作者：

Johnson, Neil W.

Semones, Marcus

Adams, Jerry L.

Hansbury, Michael

Winkler, Jim

机构：

[1] GlaxoSmithKline, Collegeville, PA 19426 USA

[2] Incyte Pharm, Wilmington, DE USA

[3] Array Biopharma, Boulder, CO USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 20期

关键词：

Tie2; kinase; angiogenesis; cancer;

D O I：

10.1016/j.bmcl.2007.08.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In an effort to understand the effect of N-alkylation of triarylimidazoles on Tie2 inhibition, ortho-substituted C-2 aryl analogs were synthesized to investigate the effect of different torsion angles on potency. This exercise resulted in the identification of a potent and selective tetrasubstituted imidazole that was efficacious in an animal model of angiogenesis. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5514 / 5517

页数：4

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