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Arzneimittelforschung 2005; 55(5): 259-264
DOI: 10.1055/s-0031-1296854
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

Synthesis and Anticonvulsant Activity of Some New Hexahydropyrimidine-2,4-dione Derivatives

Ebubekir Septioğlu
Hacettepe University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Ankara, Turkey
,
Mutlu Dilsiz Aytemir
Hacettepe University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Ankara, Turkey
,
Ünsal Çalış
Hacettepe University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Ankara, Turkey
› Author Affiliations
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Publication History

Publication Date:
23 December 2011 (online)

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Summary

In this study, twelve new hexahydropyrimidine-2,4-dione derivatives were synthesized and screened for their anticonvulsant activities. All the compounds (7a-l) which have 6-arylhexahydropyrimidine-2,4-dione and N,N-disubstituted dithiocarbamate structures were prepared by the reaction with appropriate 3-(2-chloroethyl)-6-arylhexahydropyrimidine-2,4-diones and the corresponding N,N-disubstituted dithiocarbamate potassium salts. The structure of the synthesized compounds was confirmed by UV, IR, 1H-NMR and elemental analysis. Their anticonvulsant activities were determined by maximal electroshock (MES), subcutaneous pentetrazol (metrazol, scMet) and rotorod toxicity tests for neurological deficits. According to the activity studies, 6-(4-chlorophenyl)hexahydropyrimidine-2,4-dione derivatives (7e-h) were found to be highly protective against MES and scMet. Neurotoxicity was not observed in any of the tested compounds.

Zusammenfassung

Synthese und Bewertung der antikonvulsiven Wirkung von neuen Hexahydropyrimidin-2,4-dionen

In dieser Arbeit wurden zwölf neue Derivate von Hexahydropyrimidin-2,4-dion hergestellt und auf antikonvulsive Wirkung untersucht. Alle Substanzen mit 6-Arylhexahydropyrimidin-2,4-dion und N,N-disubstituiertem Dithiocarbamat (7a-7l) wurden durch Reaktion mit 3-(2-Cloroethyl)-6-arylhexahydropyrimidin-2,4-dion und den entsprechenden N,N-disubstituierten Dithiocarbamat-Kaliumsalzen gewonnen. Die Strukturaufklärung der synthetisierten Verbindungen erfolgte mittels UV, IR, 1H-NMR-Spektroskopie sowie durch Elementaranalyse. Die antikonvulsive Wirkung wurde in MES- (Maximal Electroshock Seiture), scMet- (subkutanes Pentetrazol, Metrazol) und Drehstab-Toxizitätstests bestimmt. Die 6-(4-Chlorophenyl)hexahydropyrimidin-2,4-dion-Derivate (7e-h) waren im MES- und scMet-Test hochwirksam. Eine Neurotoxizität wurde bei keiner der untersuchten Verbindungen beobachtet.

Key words

Antiepileptic drugs - 6-Arylhexahydropyrimidine-2,4-diones, anticonvulsant activity, S-alkylation, synthesis - Carbamodithioic acid esters