Design and synthesis of a second series of triazole-based compounds as potent dual mPGES-1 and 5-lipoxygenase inhibitors

被引：41

作者：

Chini, Maria Giovanna ^{[1
]}

De Simone, Rosa ^{[1
]}

Bruno, Ines ^{[1
]}

Riccio, Raffaele ^{[1
]}

Dehm, Friederike ^{[2
]}

Weinigel, Christina ^{[3
]}

Barz, Dagmar ^{[3
]}

Werz, Oliver ^{[2
]}

Bifulco, Giuseppe ^{[1
]}

机构：

[1] Univ Salerno, Dept Pharmaceut & Biomed Sci, I-84084 Fisciano, SA, Italy

[2] Univ Jena, Inst Pharm, D-07743 Jena, Germany

[3] Univ Hosp Jena, Inst Transfus Med, D-07743 Jena, Germany

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 54卷

关键词：

Triazole-based inhibitors; In silico screening; mPGES-1; 5-Lipoxygenase; PROSTAGLANDIN-E SYNTHASE-1; UNDERSTANDING MICROSCOPIC BINDING; E-2; SYNTHASE-1; ANTIINFLAMMATORY DRUGS; THERAPEUTIC TARGET; CATALYZED REACTION; STRUCTURAL BASIS; CYCLOOXYGENASE-2; IDENTIFICATION; BIOSYNTHESIS;

D O I：

10.1016/j.ejmech.2012.05.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Microsomal prostaglandin E-2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO) are pivotal enzymes in the biosynthesis of the pro-inflammatory PGE(2) and leukotrienes, respectively. The design and synthesis of a second series of mPGES-1 inhibitors based on a triazole scaffold are described. Our studies allowed us to draw a tentative SAR profile and to optimize this series with the identification of compounds 10, 11 and 14-15 which displayed potent mPGES-1 inhibition in a cell-free assay. In addition, compounds 5, 10, 12 and 14-16 also blocked 5-LO activity in cell-free and cell-based test systems, emerging as very promising candidates for the development of safer and more effective anti-inflammatory drugs. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：311 / 323

页数：13

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