Selective benzimidazole inhibitors of the antigen receptor-mediated NF-κB activation pathway

被引：14

作者：

Okolotowicz, Karl J. ^{[1
]}

Shi, Ranxin ^{[2
]}

Zheng, Xueying ^{[1
]}

MacDonald, Mary ^{[1
]}

Reed, John C. ^{[2
]}

Cashman, John R. ^{[1
]}

机构：

[1] Human BioMol Res Inst, San Diego, CA 92121 USA

[2] Burnham Inst Med Res, La Jolla, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Nf-kappa B; Benzimidazoles; Antigen receptor-mediated; Library synthesis; Medicinal chemistry optimization; SIGNALS;

D O I：

10.1016/j.bmc.2010.01.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Dysregulated antigen receptor-mediated NF-kappa B activation can contribute to development of autoimmunity, chronic inflammation, and malignancy. A chemical biology screening strategy has identified a substituted benzimidazole that selectively inhibits antigen receptor-mediated NF-kappa B activation without blocking other NF-kappa B activation pathways. A library of analogs was synthesized and the structure-activity relationship and metabolic stability for the series is presented. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1918 / 1924

页数：7

共 20 条

[1]

Anisimova V. A., 2007, Khimiko-Farmatsevticheskii Zhurnal, V41, P9

[2] Nicotine-related alkaloids and metabolites as inhibitors of human cytochrome P-450 2A6 [J].