Synthesis and Biological Evaluation of New imidazo[1,2-a]pyridine Derivatives as Selective COX-2 Inhibitors

Author(s): Mahsa Azami Movahed, Bahram Daraei, Afshin Zarghi

Journal Name: Letters in Drug Design & Discovery

Volume 13 , Issue 8 , 2016

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Graphical Abstract:


The close structural similarity between cyclooxygenase (COX) isoforms and also the lack of potent selective COX-2 inhibitors with low side effects, stimulate the development of new highly selective COX-2 inhibitors. In this study, a group of imidazo[1,2-a]pyridines was designed, synthesized and investigated to identify potent and selective COX-2 inhibitors. In vitro COX inhibition assay showed that all derivatives were selective COX2 inhibitors with IC50 values in the highly potent 0.07-0.18 µM range and COX-2 selectivity indexes (SI) in 57-217 range. 2-(4- (methylsulfonyl)phenyl)-3-(morpholinomethyl)H-imidazo[1,2-a]pyri-dine (6f) which possessing p-methylsulfonyl phenyl at C-2 of imidazo[1,2-a]pyridine ring, exhibited the highest COX-2 inhibitory selectivity and potency. Molecular modeling and docking studies indicated that synthesized compounds have a binding similar to that of the known inhibitor SC- 558 and also methylsulfonyl group can be inserted into the secondary pocket of COX-2. The ability of synthesized compounds for inhibition of platelet aggregation was also determined. Our results demonstrated that 6f was the most potent platelet aggregation inhibitor as well.

Keywords: Cyclooxygenase-2 inhibition, platelet aggregation inhibitor, imidazo[1, 2-a]pyridines, molecular modeling, synthesis.

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Article Details

Year: 2016
Page: [793 - 799]
Pages: 7
DOI: 10.2174/1570180813666160613090944
Price: $65

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