Synthesis of New Antimalarial Agents.

The study presented in this report is concerned with the preparation of a peroxides based on qinghaosu, b peptide derivatives of primaquine, and c thymidylate synthetase inhibitors as potentially new antimalarial agents. During the first year of this study, twelve 12 target compounds were prepared and submitted for antimalarial evaluation. The twelve compounds included eight 8 qinghaosu analogs, one 1 primaquine derivative and three 3 thymidylate synthetase inhibitors. Two of the qinghaosu analogs and all three of the thymidylate synthetase inhibitors were evaluated in the malaria in vitro drug screen. The qinghaosu analogs showed reasonable activity in this screen, whereas the thymidylate synthetase inhibitors were inactive. The primaquine peptide showed sufficient activity in the preliminary prophylactic screen to warrant its submission to the monkey P. cynomolgi screen.