Studies On Chemical Structure Modification Of Nonsteroidal Anti-inflammatory Drug Felbinac

Objective:Through simple chemical structure modification method, two aspects of structural modification of 4-Biphenylacetic acid, one enhancement of biphenyl ethanoic acid on COX-2 selective inhibitor to reduce the drug’s gastrointestinal tract such areas as non-steroidal anti-inflammatory drugs side-effects, reduce the two are on the molecular structure of the carboxyl of the gastrointestinal tract directly stimulate, Synthesized three derivatives of 4-Biphenylacetic acid and the three synthetic compounds process optimization experiments to determine the optimum synthesis processMethods:First of all, Take the 4-Biphenylacetic acid, the chlorosulforic acid, the strong ammonia water as raw materials, after the sulfonylation and the ammonolysis responded that synthesizes 4’-sulfuryl amidogen-4-biphenylacetic acid; Take the 4-Biphenylacetic acid, the chlorosulforic acid, the methylamine peroxide solution as raw materials, after the sulfonylation and the ammonolysis responded that synthesizes4’-methylamine sulfuryl-4-biphenylacetic acid; Take the 4-Biphenylacetic acid and the eugenol as raw material, DCC are the dehydrator, DMAP are the catalyst, the methylene chloride as the resolver after the esterification responded that synthesized 4-biphenyl ethanoic acid-2’-methoxy-4’-(2-allyls) the phenyl ester, And through Pope (UV、IR、1H NMR、13C NMR、MS) the data, carries on the analysis to three goal member’s structure.. Utilizes the ultraviolet spectrophotometric method to determine theλmax of he three objectives products; Finally carries on the orthogonal optimization experiment to three goal members, has carried on a more comprehensive inspection and the improvement to their synthesis craft.Result:after pope structural analysis has confirmed the molecular structure of the three objectives were correct and optimized by orthogonal experiments to determine the best synthesis of the synthesis process.4’-sulfuryl amidogen 4-biphenylacetic acid’sλmax was 267nm and the mp was 242.2-243.5℃; 4’-methylamine sulfuryl-4-biphenylacetic acid’sλmax was 269nm and the mp was 199.5-200.5℃; 4-biphenylacetic acid-2’-methoxy-4’-allyls-phenyl ester’sλmax was 253nm and the mp was 60.4-61.7℃.