Synthesis and evaluation of anticonvulsant activities of some bis Mannich bases and corresponding piperidinols.
Some acetophenone derived bis Mannich bases (B1-B5) and piperidinols (C1, C4), which are the structural isomers of B1 and B4, and also quaternary piperidine derivative C6 were synthesized and studied for anticonvulsant activity. Of the compounds, C6 was reported for the first time. Chemical structures of the compounds were confirmed by UV, IR, 1H-NMR, 13C-NMR, mass spectra and elemental analysis. Their anticonvulsant activities were determined by maximal electroshock (MES), subcutaneous metrazol (scMet) tests and rotarod test for neurological deficits. According to the activity studies, B2, B4, C1 and C4 derivatives were found to be protective against MES at 30 mg/kg and above. B1, B2, B3, B4, C4 and C6 derivatives were found to be protective against scMet. at different dose levels ranging from 30 to 300 mg/kg. Since no neurotoxicity was detected for the compounds B4 and C4, they seem to be candidate compounds for further synthesis and in vivo studies for their potential anticonvulsant activity.
Gul
Halise Inci
HI
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey. incigul@mailcity.com
Calis
Unsal
U
Vepsalainen
Jouko
J
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D003292:Convulsants / Q000494:pharmacology; D003500:Cyclization; D015195:Drug Design; D004597:Electroshock; D007202:Indicators and Reagents; D008297:Male; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000523:psychology; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D004856:Postural Balance / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D003292:Convulsants; D007202:Indicators and Reagents; D008352:Mannich Bases; D010880:Piperidines; D010433:Pentylenetetrazole