Synthesis, anticonvulsant properties and pharmacokinetic profile of novel 10,11-dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide derivatives

European Journal of Medicinal Chemistry
D A LearmonthPatrício Soares-da-Silva

Abstract

A series of novel derivatives of oxcarbazepine (5), 10,11-dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide was synthesised and evaluated for their anticonvulsant activity and sodium channel blocking properties. The oxime 8 was found to be the most active compound from this series, displaying greater potency than its geometric isomer 9 and exhibiting also the highest protective index value. Importantly, the metabolic profile of 8 differs from the already established dibenz/b,f/azepine-5-carboxamide drugs such as 1 and 5 which undergo rapid and complete conversion in vivo to several biologically active metabolites. In contrast 8 is metabolised to only a very minor extent leading to the conclusion that the observed anti-convulsant effect is solely attributable to 8. It is concluded that 8 may be as effective as 1 and 5 at controlling seizures and that the low toxicity and consequently high protective index should provide the compound with an improved side-effect profile.

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Jan 1, 1985·Clinical Pharmacokinetics·M EichelbaumL Bertilsson
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Citations

Nov 6, 2010·Der Nervenarzt·B J SteinhoffA S Wendling
Nov 10, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luca VaghiAndrea Penoni
Jan 25, 2011·Bioorganic & Medicinal Chemistry·Kevin K-C LiuJin Li

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