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

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

Volume: 13 Issue: 8

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

Affiliation:

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

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.

Cite this article as:

Movahed Azami Mahsa, Daraei Bahram and Zarghi Afshin, Synthesis and Biological Evaluation of New imidazo[1,2-a]pyridine Derivatives as Selective COX-2 Inhibitors, Letters in Drug Design & Discovery 2016; 13 (8) . https://dx.doi.org/10.2174/1570180813666160613090944