Research On Phosphorothioate Synthesis And Stability Of Cytoprotectant

S-[2-(3-Aminopropyl) amino]ethyl]dihydrogen phosphorothioate(amifostine,WR-2721) and S-[3-(3-methylaminopropyl)-aminopropyl]phosphorothioate(WR- 151327)are a kind of cytoprotectant.They are injected for protceting patients against cytotoxicity of radiotherapy and chemotherapy so that improve the viability.The derivative of Amifostine 2-[(aminopropyl )]aminoethanethiol can be administered in combination with other antiretroviral agents employed to treat HIV infection.Such combination therapies is that lower doses of the other antiretroviral agents can potentially be administered while achieving a satisfactory level of antiretroviral efficacy.Such lower dosages can be particularly advantageous for antiretroviral drugs known to have cytotoxicity.And the newtype drug phosphorothioate has been hot researched all over the world.The optimum conditions of amifostine synthesis were obtained by the methods of 4 factors and 3 levels orthogonal test.The optimum technological conditions were:The reaction temperature was 24℃,DMSO was adopted as solvent,the mole ratio of sodium thiophosphate and 2-(3-aminopropylamino)ethyl bromide dihyrobromide is 1.1:1,the concentration of sodium thiophosphate in water is 1000 mmol/1.And the yeild is 91.2%,and the purity is 89.8%. S-[3-(3-methylaminopropyl)aminopropyl]phosphorothioate was synthesized by six steps with the raw material of acrylonitrile and achieved the total yield of 8.8%,and the purity is more than 96%.The metabolites of WR-2721 and WR-151327 were synthesized.All synthesized compounds were characterized by means of ~1H-NMR.The test of antioxidant activity by the elimination of DPPH radical showed that 2-[(aminopropyl)]aminoethanethiol(WR-1065) dihydrochloride have a good antioxidation activity.In this article,we have studied the stability of amifostine and amifostine for injection,and provided science to manufacture,pack,stockpile and transport.