Synthesis and anticonvulsant evaluation of some novel (thio)semicarbazone derivatives of arylalkylimidazole

Ünsal Çaliş; Septioğlu SeptioğluEbubekir; Mutlu Dilsiz Aytemir

doi:10.1055/s-0031-1296206

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2011; 61(6): 327-334
DOI: 10.1055/s-0031-1296206

CNS-active Drugs · Hypnotics · Psychotropics · Sedatives

Editio Cantor Verlag Aulendorf (Germany)

Synthesis and anticonvulsant evaluation of some novel (thio)semicarbazone derivatives of arylalkylimidazole

Ünsal Çaliş

¹Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey

,

Septioğlu SeptioğluEbubekir

¹Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey

,

Mutlu Dilsiz Aytemir

¹Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey

› Author Affiliations

Abstract

A number of novel 2-(1H-imidazole-1-yl)-1-aryl-substituted ethane-1-one N-substi-tuted phenyl(thio)semicarbazones (1-14) were synthesized to test for their anticonvulsant activity against the two seizure models, maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ). Title compounds were prepared by the reaction of appropriate (thio)semicarba-zides with ketones. Neurotoxicity was screened by the rotarod test. The structure of compounds was confirmed by elemental analysis results and the spectroscopic techniques such as IR, ¹H-NMR, ¹³C-NMR, ESI-MS and HRMS. As a result of activity studies, when the thiosemicar-bazone compounds were compared at different doses, 2-(1H-imidazole-1-yl)-1-(2-naphthyl)ethane-1-one N-(3-chloro-phenyl)thiosemicarbazone (3) and 2-(1H-imidazole-1-yl)-1-(2-biphenyl)ethane-1-one N-(4-fluorophenyl)thiosemicarba-zone (12) were found selective and highly active compounds against MES-induced seizures after 0.5 h and 4 h, respectively. Beside this, 2-(1H-imidazole-1-yl)-1-(1-biphenyl)ethane-1-one N-(4-methylphe-nyl)thiosemicarbazone (14) was the most active compound in the scPTZ-induced seizure test after 4 h. The 2,4-dichloro-phenyl (9) and 2-fluorophenyl (10) substituted biphenyl derivatives of thiosemi-carbazone compounds showed neurotoxicity at higher doses

Key words

Anticonvulsant activity - Arylalkylimidazole - Semicarbazone - Synthesis - Thiosemicarbazone

Full Text

References

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