Investigation of the synthesis and cyclooxygenase inhibitor effects of some new substitute triazinylthioether derivatives

1,2,4-triazine derivatives are known to have a wide range of biological activities including anti-inflammatory, analgesic, and anticancer activities. New COX inhibitors are being developed to reduce the side effects of drugs used as COX inhibitors and to increase selectivity among the enzyme subtypes. In this study, at first thiosemicarbazide were reacted with benzyl derivatives to obtain 1,2,4-triazin-3-thiones where these products further reacted with chloroacetylaminothiazoles to reach new 20 triazinythioether derivatives. The structure s and purity of the resulting compounds was determined by IR (infrared), NMR (nuclear magnetic resonance), Mass spectral data and elemental analysis. The COX inhibitory activities of these compounds were investigated and active compund binding site relations were analyzed by molecular modelling studies. Compounds 11-15 showed potent inhibitory activity on COX isoenzymes. The selective effect of Compound 11 on COX-2 isoenzyme was found to be higher. Keywords: 1,2,4-triazine, COX inhibitor, Antiinflammatory, Triazinylthioether, Molecular modelling