Synthesis of Substituted Piperazines and Related Compounds as Antimalarials.

摘要

This report summarized the chemistry and the antimalarial activity of one hundred compounds prepared and submitted to the U.S. Army Medical R and D Command. The finding of activity of RM-682 (AX-88991) 1-(4-methoxycinnamoyl-4-(5-phenyl-4-oxo-2-oxazolin-2-yl) piperazine in mice infected with Plasmodium berghei prompted the preparation of a proposal and then a contract to Abbott to prepare related compounds. Structure variations on the (4-oxo-2-oxazolin-2-yl) piperazine and the antimalarial activity of the active compounds are reported. The chemistry and the proof of structure of some of the compounds are discussed. (The structures of twenty-eight compounds closely related to RM-682 (AX-88991) are shown). The antimalarial activity of the six compounds having activity against P. berghei infections are shown. Four of the compounds are closely related to the lead compound. 4-Halogen or 4-methoxy substitution on phenyl group of pemoline resulted in activity greater than or comparable to that of (AX-88991). Replacement of the 4-CH3O group in the cinnamoyl moiety by 4-CF3O resulted in loss of activity. The general procedures used for the preparation of the compounds submitted are also described.