<abstract xmlns="http://www.w3.org/1999/xhtml"><p>During the last fifteen years, semicarbazones have been extensively investigated for their anticonvulsant properties. 4-(4-Flurophenoxy) benzaldehyde semicarbazone (C0102862, V102862) was discovered as a lead molecule and is being developed as a potent antiepileptic drug, with maximal electroshock (MES) <italic>ED</italic>50 of <italic>i.p. </italic>12.9 mg kg-1. In MES (oral screen), this compound has a protective index (<italic>PI </italic>= <italic>TD</italic>50/<italic>ED</italic>50 > 315) higher than carbamazepine (<italic>PI </italic>101), phenytoin (<italic>PI </italic>> 21.6) and valproate (<italic>PI</italic> 2.17). The compound is a potent sodium channel blocker. Other semicarbazones have demonstrated activity in various chemoshock screens, like subcutaneous pentylenetetrazole, subcutaneous strychnine, subcutaneous picrotoxin and subcutaneous bicculine. Semicarbazones are also GABA-transaminase inhibitors. Extensive structure- -activity relationship has demonstrated that F, Cl, Br and NO2 substituents in the arylhydrophobic pocket and a hydrogen bonding domain (HBD) are generally found in active anticonvulsant agents.</p></abstract>

During the last fifteen years, semicarbazones have been extensively investigated for their anticonvulsant properties. 4-(4-Flurophenoxy) benzaldehyde semicarbazone (C0102862, V102862) was discovered as a lead molecule and is being developed as a potent antiepileptic drug, with maximal electroshock (MES) ED50 of i.p. 12.9 mg kg-1. In MES (oral screen), this compound has a protective index (PI = TD50/ED50 > 315) higher than carbamazepine (PI 101), phenytoin (PI > 21.6) and valproate (PI 2.17). The compound is a potent sodium channel blocker. Other semicarbazones have demonstrated activity in various chemoshock screens, like subcutaneous pentylenetetrazole, subcutaneous strychnine, subcutaneous picrotoxin and subcutaneous bicculine. Semicarbazones are also GABA-transaminase inhibitors. Extensive structure- -activity relationship has demonstrated that F, Cl, Br and NO2 substituents in the arylhydrophobic pocket and a hydrogen bonding domain (HBD) are generally found in active anticonvulsant agents.

Semicarbazone – a versatile therapeutic pharmacophore for fragment based anticonvulsant drug design

Department of Pharmacy, Saroj Institute of Technology and Management Ahimamau Lucknow-226002 (U.P.), India

Acta Pharmaceutica

During the last fifteen years, semicarbazones have been extensively investigated for their anticonvulsant properties. 4-(4-Flurophenoxy) benzaldehyde...

Semicarbazone – a versatile therapeutic pharmacophore for fragment based anticonvulsant drug design

Publié en ligne: 06 nov. 2012

Pages: 263 - 286

DOI: https://doi.org/10.2478/v10007-012-0030-1

Mots clés
semicarbazone, anticonvulsant, Na+ channel blocker

This content is open access.

Semicarbazone – a versatile therapeutic pharmacophore for fragment based anticonvulsant drug design

Publié en ligne: 06 nov. 2012

Pages: 263 - 286

DOI: https://doi.org/10.2478/v10007-012-0030-1

Mots cléssemicarbazone, anticonvulsant, Na+ channel blocker

This content is open access.

Mots clés
semicarbazone, anticonvulsant, Na+ channel blocker