Design,synthesis and biological evaluation of new 1,4-dihydropyridine (DHP) derivatives as selective cyclooxygenase-2 inhibitors

As a continuous research for discovery of new cox-2 inhibitors,chemical synthesis,in vitro biological activity and molecular docking study of a new group of 1,4-dihydropyridine (dhp) derivatives were presented. novel synthesized compounds possessing a cox-2 so2me pharmacophore at the para position of c-4 phenyl ring,different hydrophobic groups (r1) at c-2 position and alkoxycarbonyl groups (coor2) at c-3 position of 1,4-dihydropyridine,displayed selective inhibitory activity against cox-2 isozyme. among them,compound 5e was identified as the most potent and selective cox-2 inhibitor with ic50 value of 0.30 μm and cox-2 selectivity index of 92. molecular docking study was performed to determine probable binding models of compound 5e. the study showed that the p-so2me-phenyl fragment of 5e inserted inside secondary cox-2 binding site (arg513,phe518,gly519,and his90). the structure-activity relationships acquired reveal that compound 5e with methyl and ethoxycarbonyl as r1 and coor2 substitutions has the necessary geometry to provide selective inhibition of the cox-2 isozyme and it can be a good basis for the development of new hits. © 2015 by school of pharmacy shaheed beheshti university of medical sciences and health services.