Studies On Design, Synthesis And Bioactivity Of Purine Carboxylic Acid, Piperazine Carboxylic Acid, Ribavirin And Thiosemicarbazones

Studies on synthesis of antibacterial drugs, antiviral drugs and antitumor drugs are a hot field in modern medicinal chemistry. In this paper, the efforts were focused on design and synthesis of 9-N-substitued purine carboxylic acid (ester), 4-N-substitued piperazine carboxylic acid, ribavirin derivatives and thisonsemicarbazones, and study on their bioactivities. A series of useful and creative results have been obtained.35 target compounds (eight compounds of 9-N-substitued purine carboxylic acid (ester), five compounds of 4-N-substitued piperazine carboxylic acid, four compounds of ribavirin analogs and eighteen compounds of thiosemicarbazones ) have been synthesized, which 32 compounds haven't been reported in literatures. Their chemical structures were confirmed by MS, IR, (1)~HNMR or elemental analysis. The synthetic methods and effect factors of the target compounds have been systematically studied. A series of convenient and efficient reactions have been developed.The synthetic methods of thiosemicarbazones have been systemically investigated, and suitable conditions were chosen. A simple eco-friendly route with high yields has been obtained under microwave irradiation. It significantly decreased in reaction time as compared with the classical methods (The reaction time using microwave irradiation shorten 16-24 times than using classical method).Furthermore, yields of these target compounds have been increased to preferable degrees, and the using volume of solvents under microwave irradiation is only quarter of classical method's.The part target compounds of preliminary investigation on the bioactivity have been carried out to test our designs. The results of bioactivity in vivo of these target compounds showed that two of the four new 5'-substitued ribavirin analogs had anti-influenza A activities in different degrees. These results had confirmed our preliminary assumption. All of these results offer some important reference to 5'-substitued ribavirin analogs antiviral drug systemically investigated in the future.