Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR

被引：57

作者：

Abdelall, Eman K. A. ^{[1
]}

Kamel, Gehan M. ^{[2
]}

机构：

[1] Beni Suef Univ, Dept Organ Pharmaceut Chem, Fac Pharm, Bani Suwayf 62514, Egypt

[2] Cairo Univ, Dept Pharmacol, Fac Vet, Cairo, Egypt

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 118卷

关键词：

Cyclooxygenase inhibitors; Celecoxib analogues; SO2NH2; pharmacophores; 15-Lipoxygenase inhibitors; Anti-inflammatory; DMFDMA; Ethyl trifloroacetate; BIOLOGICAL EVALUATION; 5-LIPOXYGENASE; CYCLOOXYGENASE; DERIVATIVES; COX-2; LEUKOTRIENES; AGENTS; PROSTAGLANDINS; INFLAMMATION; MEDIATORS;

D O I：

10.1016/j.ejmech.2016.04.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 mu M against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 mu M) and meclofenamate sodium (5.64 mu M). (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：250 / 258

页数：9

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