Accession Number : ADA015518

Title :   Synthesis of Substituted Piperazines and Related Compounds as Antimalarials.

Descriptive Note : Final rept. 1 Jun 72-31 May 74,


Personal Author(s) : Geiszler,A. O.

Report Date : 22 JAN 1975

Pagination or Media Count : 33

Abstract : 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.

Descriptors :   *Antimalarials, *Chemotherapeutic agents, Synthesis(Chemistry), Nitrogen heterocyclic compounds, Oxygen heterocyclic compounds, Drugs, Malaria, Parasitic diseases

Subject Categories : Pharmacology
      Organic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE