Septioglu Ebubekir, Aytemir Mutlu Dilsiz, Caliş Unsal
Hacettepe University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Ankara, Turkey.
Arzneimittelforschung. 2005;55(5):259-64.
In this study, twelve new hexahydropyrimidine-2,4-dione derivatives were synthesized and screened for their anticonvulsant activities. All the compounds (7a-1) which have 6-arylhexahydropyrimidine-2,4-dione and N,N-disubstituted dithiocarbamate structures were prepared by the reaction with appropriate 3-(2-chloroethyl)-6-arylhexahydropyrimidine-2,4diones and the corresponding N,N-disubstituted dithiocarbamate potassium salts. The structure of the synthesized compounds was confirmed by UV, IR, 1H-NMR and elemental analysis. Their anticonvulsant activities were determined by maximal electroshock (MES), subcutaneous pentetrazol (metrazol, scMet) and rotorod toxicity tests for neurological deficits. According to the activity studies, 6-(4-chlorophenyl)hexahydropyrimidine-2,4-dione derivatives (7e-h) were found to be highly protective against MES and scMet. Neurotoxicity was not observed in any of the tested compounds.
在本研究中,合成了12种新的六氢嘧啶-2,4-二酮衍生物,并对其抗惊厥活性进行了筛选。所有具有6-芳基六氢嘧啶-2,4-二酮和N,N-二取代二硫代氨基甲酸盐结构的化合物(7a-1)均通过与适当的3-(2-氯乙基)-6-芳基六氢嘧啶-2,4-二酮和相应的N,N-二取代二硫代氨基甲酸钾盐反应制备。通过紫外光谱(UV)、红外光谱(IR)、1H-核磁共振(1H-NMR)和元素分析确定了合成化合物的结构。通过最大电休克(MES)、皮下注射戊四氮(五甲烯四氮唑,scMet)和转棒试验对神经功能缺损的毒性测试来测定它们的抗惊厥活性。根据活性研究,发现6-(4-氯苯基)六氢嘧啶-2,4-二酮衍生物(7e-h)对MES和scMet具有高度保护作用。在任何测试化合物中均未观察到神经毒性。