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  • Title: Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities.
    Author: Abdel-Aziz M, Abuo-Rahma Gel-D, Hassan AA.
    Journal: Eur J Med Chem; 2009 Sep; 44(9):3480-7. PubMed ID: 19268406.
    Abstract:
    Substituted carboxylic acid hydrazides 1a-d reacted with ethenetetracarbonitril 2 in dimethyl formamide with the formation of diacylhydrazines 4a-d and 5-amino-1-substituted pyrazole-3,3,4-tricarbonitriles 5a-d. On the other hand, 1a-d reacted with diethyl (E)-2,3-dicyanobutenedioate 3 to give oxadiazole derivatives 10a-d and pyrazolone derivatives 11a-d, respectively. The prepared compounds 4a-d, 5a-d and 11a-d were evaluated each for antidepressant activity using tail suspension behavioral despair test and anticonvulsant activity against PTZ induced seizures in mice. Compounds 4a and 4b induced markedly antidepressant activity compared to imipramine, and their activities as antidepressant nearly equal twice the activity of imipramine at 10 mg kg(-1) dose level. On the other hand, compounds 11b, 11a and 11d exhibited remarkable protective effect against clonic seizures induced by i.p. injection of PTZ at a dose level of 20 mg kg(-1). The results of anticonvulsant activity are nearly close to phenobarbital sodium at a dose level of 30 mg kg(-1) and more potent than phenytoin sodium at a dose level of 30 mg kg(-1).
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