Synthesis of novel pyrazole-thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors

被引：43

作者：

Alegaon, S. G. ^{[1
]}

Hirpara, M. B. ^{[1
]}

Alagawadi, K. R. ^{[1
]}

Hullatti, K. K. ^{[2
]}

Kashniyal, K. ^{[1
]}

机构：

[1] KLE Univ, KLES Coll Pharm, Dept Pharmaceut Chem, Belgaum 590010, Karnataka, India

[2] KLE Univ, KLES Coll Pharm, Dept Pharmacognosy, Belgaum 590010, Karnataka, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 22期

关键词：

Pyrazoles; Thiadiazole; COX-1 and COX-2; Cytotoxicity; Docking; Drug likeness; BIOLOGICAL EVALUATION; MOLECULAR DOCKING; DERIVATIVES; DISCOVERY; DESIGN; SERIES; ACID;

D O I：

10.1016/j.bmcl.2014.08.062

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A series of 1,3,4-trisubstituted pyrazole derivatives (3a-f), (4a-f), and (5a-f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, H-1 NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC50 of 1.33-17.5 mu M. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC50 = 1.33 mu M), with a significant selectivity index (SI >60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole-thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5324 / 5329

页数：6

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