The Synthesis And Characterization Of Tiopronin Prodrugs

Tiopronin is a novel sulfhydryl glycin drug. The chemical name for the N-(2-mercapto propionyl)-glycine. For the treatment of various types of chronic hepatitis, fatty liver, cirrhosis and other liver diseases, the metal poisoning also save function. In addition to the radiotherapy treatment has certain auxiliary function. China’s market has been the dosage of enteric-coated tablets, injections with Tiopronin injection.The effect of the drug is significant, but in clinical use is not convenient, the intravenous drip for specialized sodium hydroxide solvent. Due to its ease of oxidation characteristics, in the storage and transportation also has certain difficulty.Experiment purpose1Selective adaptation of carrier modification of tiopronin, screened in vitro basic stable compounds.2To meet the conditions of the compounds were synthesized research, process optimization.3The synthesized product structural identification, measurement, IR, melting point of carbon hydrogen spectrum, spectrum analysis.Experimental method and results1With acyl chloride as acylating reagent, using benzoyl chloride with Tiopronin in three-the organic alkali as catalyst under the conditions of reaction. Find, benzoyl chloride and the optimum reaction conditions of Tiopronin for benzoyl chloride:tiopronin is1.3, catalyst dosage three ethylamine:tiopronin is1.1, reaction time was3hours, reaction temperature20C.2The same screening methodology for the discovery of methyl benzoyl chloride with Tiopronin optimum catalyst for DMAP, at the same time, determine the optimum conditions for the feed ratio (methyl benzoyl chloride:tiopronin) is1.4, the dosage of catalyst (DMAP: tiopronin))1.2, reaction time is1hour, reaction temperature5C. Anisoyl chloride with Tiopronin optimum reaction conditions for the feed ratio (Anisoyl chloride:tiopronin) is1.5, the dosage of catalyst (DMAP:tiopronin))1.1, reaction time was1.5hours, reaction temperature5C.3Through the determination of melting point, TLC thin layer plate, HPLC spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectra of hydrogen and carbon structure identification, to determine the product for our target compounds.4For the products after processing of simple, found using petroleum ether as solvent recrystallization can achieve good results.5The target compounds stability test, found3drugs in3months, the appearance characters of PH had no significant change.The experimental conclusion1The synthesis method is applied to the general synthesis laboratory, experimental conditions are simple, easy to follow-up research and is convenient for industrial expansion.2through a variety of ways, for identification, to determine the synthetic compounds as our target compounds.3after the processing step is simple, without special treatment.4experiments confirmed that the compounds in vitro placed chemical properties, appearance, PH, there are no significant changes in content. So these three kinds of compounds in vitro are stable, as we further in vivo experiment well foundation.