Aminoalkanolic derivatives of xanthone with potential antiepileptic activity.
Synthesis, physicochemical and anticonvulsant properties of some aminoisopropanoloxy derivatives of 2-xanthone are described. The compounds were prepared by the amination of 2-[(2,3-epoxy)-propoxyl]-xanthone or 2-(3-chloro-2-hydroxy-propoxy)-xanthone. The obtained compounds were evaluated for anticonvulsant activity in the maximal electroshock (MES)- and subcutaneous pentylenetetrazole (scMet)-induced seizures and for neurotoxicity in the rotorod test in mice and rats. The most promising compounds seem to be the 3-(tert.-butyl-amino) (3), 3-[N-methyl-(tert.-butyl)-amino] (12) and 3-[4-(benzyl)-1-piperazinyl (5) substituted 2-hydroxy-1-(2-xanthonoxy)-propane from which 3 and 5 were active in both the anticonvulsant tests. The protective index (TD50/ED50) in MES in mice for 3 and valproate, as for 12 and phenytoin or carbamazepine, is similar.
Marona
H
H
Department of Chemical Technology of Drugs, Jagiellonian University, Kraków, Poland.
Górka
Z
Z
Szneler
E
E
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004597:Electroshock; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D014966:Xanthenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D044004:Xanthones
D000927:Anticonvulsants; D014966:Xanthenes; D044004:Xanthones; C009689:xanthone; D010433:Pentylenetetrazole