A series of new 3-hydroxy-6-hydroxymethyl-2-substituted 4H-pyran-4-one derivatives were synthesized as potential anticonvulsant compounds. Mannich compounds were prepared by the reaction of appropriate substituted piperazine derivatives with kojic acid and formaline. The structure of the synthesized compounds was confirmed using the elementary analysis results and spectroscopic techniques such as IR, 1H-NMR and ESI-MS. Anticonvulsant activities of the synthesized compounds were examined by maximal electroshock (MES) and subcutaneous Metrazol (scMet) induced seizure tests. Neurotoxicity was determined by the rotorod toxicity test. All these tests were performed according to procedures of the Antiepileptic Drug Development (ADD) program. According to the activity studies, 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-3-hydroxy-6-hydroxymethyl-4H-pyran-4-one (compound 11) against MES seizures and 3-hydroxy-6-hydroxymethyl-2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-4H-pyran-4-one (compound 7) against scMet seizures were determined to be the most active compounds at all doses without neurotoxicity.

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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

The title compound, C19H24ClNO2, was synthesized and characterized by single‐crystal X‐ray diffraction. The adamant­yl and benzene groups are bridged by an imine group, with a C—C=N—C torsion angle of −178.2 (2)°. Weak C—H⋯O and C—H⋯π inter­actions are found in the crystal packing.

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-2,4diones and the corresponding N,N-disubstituted dithiocarbamate potassium salts. The structure of the synthesized compounds was confirmed by UV, IR, 1 H-NMR and elemental analysis. Their anticonvulsant activities were determined by maximal electroshock (MES), subcutaneous pentetrazol (metrazol, scMet) and ro-Zusammenfassung Synthese und Bewertung der antikonvulsiven Wirkung von neuen Hexahydropyrimidin-2,4-dionen In dieser Arbeit wurden zwölf neue Derivate von Hexahydropyrimidin-2,4dion 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, 1 H-NMR-Spektroskopie sowie durch Elementaranalyse. Die antikonvulsive Wirkung wurde in torod 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. MES-(Maximal ElectroshockSeiture), 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 Arzneim.-Forsch./Drug Res. 55, No. 5, 259−264 (2005) Arzneim.-Forsch./Drug Res. 55, No. 5, 259−264 (2005) Septioglu et al. − Hexahydropyrimidine-2,4-dione derivatives