Antimalarials. Synthesis and antimalarial activity of 1 (4 methoxycinnamoyl) 4 (5 phenyl 4 oxo 2 oxazolin 2 yl)piperazine and derivatives

Article abstract of DOI:10.1021/jm00246a009

The preparation and activity against Plasmodium berghei of derivatives of 1 (4 methoxycinnamoyl) 4 (5 phenyl 4 oxo 2 oxazolin 2 yl)piperazine are described. Replacement of the cinnamoyl group was accomplished by acylation or alkylation of 1 (5 phenyl 4 oxo 2 oxazolin 2 yl)piperazine. Modifications of the 5 phenyl group were prepared either by a sequence of reactions involving mandelic ester pemoline piperazine pemoline or by the reaction of 5 aryl 2 thio 2,4 oxazolidinedione with piperazine or N substituted piperazines. In a similar manner, pemoline was allowed to react with N arylpiperazine, hexahydro 1H 1,4 diazepine, and 2,6 dimethylpiperazine to provide N arylpiperazine pemoline derivatives and variations in the piperazine moiety. Several compounds in which the 2 oxazolin 4 one ring was replaced with other heterocyclic rings were prepared as were several open chain analogs. Five compounds (three of them substituted in the para position of the 5 phenyl group and two N arylpiperazine pemoline derivatives) were found to be active against Plasmodium berghei. The remaining active compound possessed changes in the cinnamoyl group and substitution on the 5 phenyl group.