Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structure of pirinixic acid

被引：24

作者：

Werz, Oliver ^{[1
]}

Greiner, Christine ^{[1
]}

Koeberle, Andreas ^{[1
]}

Hoernig, Christina ^{[2
]}

George, Sven ^{[2
]}

Popescu, Laura ^{[2
]}

Syha, Ivollne ^{[2
]}

Schubert-Zsilavecz, Manfred ^{[2
]}

Steinhilber, Dieter ^{[2
]}

机构：

[1] Univ Tubingen, Dept Pharmaceut Analyt, Inst Pharmaceut, D-72076 Tubingen, Germany

[2] Univ Frankfurt, Inst Pharmaceut Chem, ZAFES, D-60438 Frankfurt, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 17期

关键词：

D O I：

10.1021/jm800588x

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of potent 5-lipoxygenase (5-LO) product synthesis inhibitors based on the structure of pirinixic acid (4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid, compound 1) is presented. Systematic profilin g, of 1, i.e., esterification of the carboxylic acid, cc-substitution, and replacement of the o-dimethylaniline by 6-aminoquinoline, leads to potent Suppressors of 5-LO product formation in activated polymorphonuclear leukocytes, exemplified by ethyl 2-[4-chloro-6-(quinoline-6-ylamino)-pyrimidin-2-ylsulfanyl]octane-1-carboxylate (6d, IC50 = 0.6 mu M). These derivatives may possess potential for intervention with inflammatory and allergic diseases.

引用

页码：5449 / 5453

页数：5

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