SYNTHESIS AND ANTICONVULSANT STUDIES OF 3-ANILINOPROPANAMIDES AND THEIR N-BENZYL DERIVATIVES
SYNTHESIS AND ANTICONVULSANT STUDIES OF 3-ANILINOPROPANAMIDES AND THEIR N-BENZYL DERIVATIVES
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Date
2008-03
Authors
IDRIS, ABDULLAHI YUNUSA
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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.
Description
A DISSERTATION SUBMITTED TO THE
POSTGRADUATE SCHOOL,
AHMADU BELLO UNIVERSITY, ZARIA
NIGERIA
IN PARTIAL FULFILLMENT FOR THE AWARD OF DOCTOR OF
PHILOSOPHY IN PHARMACEUTICAL AND MEDICINAL CHEMISTRY
DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL
CHEMISTRY
AHMADU BELLO UNIVERSITY, ZARIA
NIGERIA.
Keywords
SYNTHESIS,, ANTICONVULSANT,, STUDIES,, 3-ANILINOPROPANAMIDES,, N-BENZYL,, DERIVATIVES