Design of acyclic triaryl olefins: a new class of potent and selective cyclooxygenase-2 (COX-2) inhibitors

被引：29
|
作者：
Uddin, MJ [1 ]
Rao, PNP [1 ]
Knaus, EE [1 ]
机构：
[1] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 08期
基金：
加拿大健康研究院;
关键词：
acyclic olefins; cyclooxygenase-2; anti-inflammatory;
D O I：
10.1016/j.bmcl.2004.01.075
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new class of acyclic 1,1-diphenyl-2-(4-methylsulfonylphenyl)-2-alkyl-1-ethenes were synthesized, via a short two-step McMurry olefination reaction and then oxidation of the thiomethyl intermediate using Oxone(, in 62-76% yield. The title compounds possess identical C-1 phenyl substituents which precludes the possibility of (Z)- and (E)-stereoisomers. 1,1-Diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene exhibited highly potent (IC50 = 0.014 muM) and selective COX-2 (Selectivity Index >7142) inhibitory activity. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1953 / 1956
页数：4
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