Synthesis Of Acylthiourea Derivatives And Optimization Of Pharmaceutical Preparations

Because of the good biological activity of thiourea compounds in insecticidal, sterilization, weeding, regulating plant growth and antitumor, many scholars pay attention to it. In recent years, the people have done a lot of research to synthesize thiourea derivatives, which had a lot of good quality But the study in the application of thiourea compounds was rarely,and little literature reported thiourea derivatives of pharmaceutical preparations and field trials. Before a new drug flow into the market, the research on its application must be especially mature. Therefore thiourea derivatives in pharmaceutical preparations and field application had important research value and broad application.In this paper, we had synthesised6kinds of acyl thiourea derivatives on the basis of research work. And we had made the bacteriostatic activity test of these compounds, get active data, as the basis of the synthesis process optimization and pharmaceutical preparations. The synthesized compound as follows:Ⅰ:N-(2,3-Dimethyl-phenyl)-N’-(methoxyl formyl) thiourea (DM)Ⅱ:4,4’-bis(3-N-methoxyformyl thioureido)-diphenyloxide (BMD)ⅢI:N-formylmethoxyl-N’-(1,3,4-thiadiazole-2-yl)thiourea (T2ZTM)Ⅳ:N-formylethoxyl-N’-(1,3,4-thiadiazole-2-yl)thiourea (T2ZTY)Ⅴ:N-p-methoxylbenzoyl-N’-(pyrimidin-2-yl)thiourea (MP)Ⅵ:N-benzoyl-N’-(4,6-dimethxoyl-pymidin-2-yl)thiourea (BDP)Bacteriostatic activity of compounds were determined by growth rate method, the experimental results show that:Antimicrobial properties is one of the best DM, T2ZTM and T2ZTY, the highest antibacterial rate of DM is63.67%, the highest antibacterial rate of T2ZTM is70.43%, and the antibacterial rate of T2ZTY can be as high as92.79%. Bacteriostatic activity of DM is stable, and bacteriostatic rate of T2ZTY is highest, So, do synthesis process optimization test and pharmaceutical preparations test with this two compounds.Determine the best process parameters through the process optimization experiment. The optimal production technology of DM are as follows:The first step reaction is70℃,2h, catalyst for1/20of the chloride (volume ratio); The second step reaction72℃,4.5h, and this two step reaction in stirring. The optimal production technology of T2ZTY are as follows:The first step reaction is70℃,2h, catalyst for1/20of the chloride (volume ratio); The second step reaction70℃,4h, and this two step reaction in stirring. Determine the drug dosage forms, solvent and emulsifier types, and the best material proportion based on DM and T2ZTY pharmaceutical preparation experiment. Ec DM material quantity as follows:DM technical was15%, Emulsifier of26%agricultural emulsifier500#and74%agricultural emulsifier700#combination was14%, Solvent n-hexane was71%, The emulsification of Ec DM is qualified after testing. Ec T2ZTY material quantity as follows: T2ZTY technical was10%, Emulsifier of26%agricultural emulsifier500#and74%agricultural emulsifier700#combination was15%, Solvent n-hexane was75%, The emulsification of Ec T2ZTY is qualified after testing.