Abstract
The 3-ANPs (A01-A10) were prepared through acid catalysed Michael addition while the N-benzyl derivatives (A11-A15) were obtained through an uncatalysed amine exchange reaction with benzylamine. The structures of these compounds were established using various spectroscopic techniques. Compounds (A01-A15) were screened in mice against maximal electroshock (MES) and subcutaneous pentylene tetrazole (scPTZ) seizure models as well as the righting reflex test for neurological deficit. All the 15 compounds were active in the MES test with A04, A05, A07 and A13 being more potent than phenytoin. Compounds A05, A06 and A11-A15 were active in both MES and scPTZ seizures models and therefore have valproate-like activity. Compound A04 is the most potent (ED50 = 0.63mg/Kg) anti-MES compound ever reported in the literature while compound A13 is the most potent (MES ED50 = 3.25mg/Kg and scPTZ ED50 = 20.40mg/Kg) in the valproate class. The results of this work agrees with Unverferth et al (1998) and Shindikar et al (2006) proposed pharmacophores for anticonvulsants active at the voltage-dependent sodium channels. The compounds mentioned above are recommended for further studies.
Abstract
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