Synthesis and Biological Evaluation of a 5-6-5 Imidazole-Phenyl-Thiazole Based α-Helix Mimetic

被引：58

作者：

Cummings, Christopher G. ^{[1
]}

Ross, Nathan T. ^{[1
]}

Katt, William P. ^{[1
]}

Hamilton, Andrew D. ^{[1
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

来源：

ORGANIC LETTERS | 2009年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

RATIONAL DESIGN; DERIVATIVES; PROTEOMIMETICS; SCAFFOLD; CDC42;

D O I：

10.1021/ol8022962

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The development of small molecules that disrupt protein-protein Interactions is a key goal in addressing a number of disease states. The cc-helix It, commonly found at protein Interaction interfaces and has been the focus of substantial small molecule mimetic efforts. One of the primary drawbacks of many small molecule alpha-helix mimetics is their hydrophobic core structures. To address this problem we have developed a novel scaffold based on a more water soluble 5-6-5 Imidazole-phenyl-thiazole core. An inhibitor of this class has been shown to disrupt the Cdc42/Dbs protein-protein Interaction at micromolar concentrations and may be useful in overcoming Cdc42-induced tumor resistance to anticancer therapies.

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页码：25 / 28

页数：4

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