The Research For The Synthesis Of Lumiracoxib And Its Analog

It is now well established that there were two major iso-forms of cyclooxygenase(cox). The constitutive enzyme, cox-1, has been well characterized and is postulated to be involved in the maintenance of essential physiological fuctions such as platelet aggregation, cy-toprotection in the stomach and the maintenance of normal kidney fuctions. A second isozyme , cox-2,has also been described and it shares about 60% sequence homology with cox-1 at the amino acid level. cox-2 has been shown to be induced significantly in vivo under inflammatory conditions .cox-2 plays a key role in pathological conditions. this has also provided a rationale for the development of selective inhibitors of cox-2 as a new class of anti-inflammatorty agents which would possess a substantially improved side effect profile. compared to current clinically available non-steroidal anti-inflammatorty drugs (NSAIDS) which inhibit both cox-1 and cox-2.Lumiracoxib is a novel cyclooxygenase-2(COX-2) selective inhibitors that has been developed as an oral formulation for the treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis, and the management of acute pain. Studies on the synthesis of Lumiracoxib have great practical value and economic benefit.The development, molecular base, Structure-activity relationship and classification of the COX-2 inhibitor as well as pharmic character , development status and trend of Lumiracoxib were reviewed in this paper. Lumiracoxib is one of the representatives COX-2 inhibitor in the second generation, we focused on the study of its synthesis, and the optimize of the key step; at one time some research was done on the preparation of its analogous.Lumiracoxib was synthesized by chloroacetylation of P-Toluidine with chloro acetylchlorid, etherification and rearragement reaction, then chloroacetylation again, cyclization reaction which is virtually F-C alkylation reaction, and ring opening reaction. The whole course ran smoothly. The yield of all steps is higher than the literature's. The overall yield reached 58.8 %.During the preparation of Lumiracoxib, adding an amount of PEG2000 when 2-chloro-N-4-methylphenylacetamide etherifying with 2-chloro-6-fluorophenol, The yield of etherification upgrades from 82.9% to 94.7%. Similarly putting in PEG2000 in the ring-opening reaction , The yield can be improved from 81% to 89.6%.