Discovery of quinazolines as a novel structural class of potent inhibitors of NF-κB activation

被引：149

作者：

Tobe, M ^{[1
]}

Isobe, Y ^{[1
]}

Tomizawa, H ^{[1
]}

Nagasaki, T ^{[1
]}

Takahashi, H ^{[1
]}

Fukazawa, T ^{[1
]}

Hayashi, H ^{[1
]}

机构：

[1] Japan Energy Corp, Pharmaceut & Biotechnol Lab, Toda, Saitama 3358502, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2003年 / 11卷 / 03期

关键词：

D O I：

10.1016/S0968-0896(02)00440-6

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：

We disclose here a new structural class of low-molecular-weight inhibitors of NF-kappaB activation that were designed and synthesized by starting from quinazoline derivative 6a. Structure-activity relationship (SAR) studies based on 6a elucidated the structural requirements essential for the inhibitory activity toward NF-kappaB transcriptional activation, and led to the identification of the 6-amino-4-phenethylaminoquinazoline skeleton as the basic framework. In this series of compounds, 11q, containing the 4-phenoxyphenethyl moiety at the C(4)-position, showed strong inhibitory effects on both NF-kappaB transcriptional activation and TNF-alpha production. Furthermore, 11q exhibited an anti-inflammatory effect on carrageenin-induced paw edema in rats. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：383 / 391

页数：9

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