Studies On Structural Modification Of Antipyretic Analgesic Acetaminophen

Objective:To put together the basis of principle and the principle of prodrug to an antipyretic and analgesic effects of acetaminophen and liver of the antipyretic analgesic effect of ferulic acid as raw material, through chemical structure modification, access to the four structural modification objects (TMI, TM2, TM3, TM4), the expectations from the selected one-2 antipyretic analgesic efficacy is not inferior to acetaminophen, the liver toxicity of acetaminophen than low structural modification of drug.Methods:First, vanillin as raw material, Doebner synthesis of ferulic acid, phenolic hydroxyl group was acetylated to protect and acetaminophen combinations synthesized esterification TM1; to vanillin as raw material, was synthesized by the bromination 5-bromo-vanillin intermediates, and its intermediates by Doebner synthesized 5-bromo-ferulic acid with acetaminophen esterification into TM2; to vanillin as raw material, mixed acid (HNO3, mixed acid) Nitrification Generation 5-nitro vanillin intermediates, and its intermediates by Doebner synthesized 5-nitro Ferulic acid,5-nitro Ferulic acid with acetaminophen combinatorial synthesis TM3; to DCC as dehydrating agent DMAP as a catalyst, will join phenylacetic acid and acetaminophen combinations synthesized by esterification TM4. Secondly, the structural modification of the product yield as an index of portfolio structure modifier TM1, TM4 molecular synthesis process optimization. Results:by spectral (UV, IR,1H-NMR,13C-NMR, MS) test data to confirm the target molecule TM1, TM4 structure and TM2, TM3 intermediate 5-bromo-ferulic and 5-nitro Ferulic acid structure right. Set TM1, TM4 best conditions of synthesis process.Conclusion:The preliminary research data for TM2, TM3 final combination of the success of the feasibility of providing for the late goal in four combinations of molecular pharmacological experiments have laid a foundation.