Molecule Design And Synthesize New COX-2 Selective Inhibitors

Cyclooxygenase-2 selective inhibitors are series of NSAIDs which are widely used in the treatment of OA and RA. The COX-2 selective inhibitors now in markets mostly have defferent extent side effect in gastroduodenal. So it is important to find out the new COX-2 selective inhibitors which have more active in anti-inflammatory and fewer side effect in gastroduodenal by molecule design and synthesis.In this text, we have collected excess of eight hundred kinds of compounds which have COX-2 slective active. All their structures were optimized by using PM3 semimpirical quantum method, and we put the dates of compounds structures and actives export to Tsar software together and build up a database for our research. We also have reviewed tricyclic COX-2 selective inhibitors and their quantitative structure-activity relationships.The structures of a new series of 1,5-Diarylimidazolescycloxygenase-2 inhibitors were calculated by using PM5 semiempirical quantum chemistry methods, the 2D-QSAR of inhibitors were studied by genetic algorithm and multiple regression method, and the 3D-QSAR of inhibitors were analyzed by S0MFA2 software. It was found that the structures of 1,5-Diarylimidazoles COX-2 inhibitors are similar to the structures of typical tricyclic cycloxygenase-2 selective inhibitors, but the results of QSAR of 1,5-Diarylimidazoles COX-2 inhibitors is different from that of typical tricyclic cycloxygenase-2 selective inhibitors such as celecoxib, there is new QSAR in 1,5-Diarylimidazoles COX-2 inhibitors.Rofecoxib and its derivatives, a new series of open-loop COX-2 inhibitors were calculated by using PM3 semiempirical quantum chemistry methods. 2D-QSAR of 11 inhibitors were studied based on Structure parameters searched from database or theory calculation and 3D-QSAR of all inhibitors were analyzed by S0MFA2 software. It was found that the structures of open-loop derivatives are similar to the structure of Rofecoxib, and the structure-activity relationships are similar to that of other COX-2 inhibitors.We have studied the synthesis of 2-chloro-6-fluoroaniline which is the intermediate of Lumiracoxib that is a kind of COX-2 selective inhibitors. Using 2-chloro-6-aminotoluene as startial material, by dizotization and fluorination, 2-chloro-6-fluorotoluene was prepared. Then It is oxidated by potassium permanganate, and the product is...