Synthesis of Some New Hydroxypyranone Derivatives and Evaluation of Their Anticonvulsant Activities
Mutlu Dilsiz AYTEMİR*^,°, Ünsal ÇALIŞ* 
* Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06100 Ankara, TURKEY.

^oCorresponding Author

Summary

In this study, Mannich bases of hydroxypyranone derivatives were synthesized by starting from kojic acid. Their anticonvulsant activities were evaluated in in vivo studies. Mannich bases were prepared by the reaction of cyclic amine derivatives with allomaltol and formaline. The chemical structure of synthesized compounds 3a-e was proven by IR, 1H-NMR, mass spectra and elementary analysis data. Anticonvulsant activities of the compounds were examined by maximal electroshock (MES) and subcutaneous Metrazol (scMet) tests. Neurotoxicity was determined by rotorod toxicity test. All these tests were performed in mice according to procedures of the Antiepileptic Drug Development (ADD) program of the National Institutes of Health (NIH). According to the activity studies, compound 3a, which is carrying 4-[(2,3-dimethylphenyl)piperazin-1-yl]methyl at 2 position on the pyranone ring, showed activity against scMet at 300 mg/kg dose at 4 h. Only compound 3b was determined to be protective against MES at 300 mg/kg dose at 0,5 h in this series. None of the synthesized compounds was observed to have neurotoxicity.

Key Words :
Hydroxypyranone derivatives, kojic acid, allomaltol,Mannich reaction, anticonvulsant activity