Herrin T R, Pauvlik J M, Schuber E V, Geiszler A O
J Med Chem. 1975 Dec;18(12):1216-23. 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.
描述了1-(4-甲氧基肉桂酰基)-4-(5-苯基-4-氧代-2-恶唑啉-2-基)哌嗪衍生物的制备及其对伯氏疟原虫的活性。通过1-(5-苯基-4-氧代-2-恶唑啉-2-基)哌嗪的酰化或烷基化来实现肉桂酰基的取代。5-苯基的修饰是通过涉及扁桃酸酯-匹莫林-哌嗪匹莫林的一系列反应，或者通过5-芳基-2-硫代-2,4-恶唑烷二酮与哌嗪或N-取代哌嗪的反应来制备的。以类似的方式，使匹莫林与N-芳基哌嗪、六氢-1H-1,4-二氮杂卓和2,6-二甲基哌嗪反应，以提供N-芳基哌嗪匹莫林衍生物以及哌嗪部分的变体。制备了几种其中2-恶唑啉-4-酮环被其他杂环取代的化合物以及几种开链类似物。发现有五种化合物（其中三种在5-苯基的对位被取代，两种为N-芳基哌嗪匹莫林衍生物）对伯氏疟原虫有活性。其余的活性化合物在肉桂酰基部分有变化且在5-苯基上有取代。
