Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties

A series of new xanthone derivatives have been synthesized and evaluated for their anticonvulsant properties in the maximal electroshock, subcutaneous metrazole tests and for neurotoxicity in the rotarod in mice, i.p. and rats, p.o. Compound 9: R,S‐2‐{2‐[(1‐hydroxybutan‐2‐yl]amino)ethoxy}‐9H‐xanthen‐9‐one and compound 12: R,S‐2‐{3‐[(1‐hydroxybutan‐2‐yl)amino]propoxy}‐9H‐xanthen‐9‐one exerted activity in rats, p.o. 2 and 4 h after administration, respectively. Therefore, metabolic stability of the compounds was evaluated with use of rat microsomes, resulting in half‐life t1/2 136 and 108 min, respectively, indicating that either the metabolites are very active or the parent compounds exert ADME properties other than metabolism which influence the late onset of activity. New xanthone derivatives were synthesized and evaluated for anticonvulsant properties and neurotoxicity in mice and rats. R,S‐2‐{2‐[(1‐hydroxybutan‐2‐yl]amino)ethoxy}‐9H‐xanthen‐9‐one and R,S‐2‐{3‐[(1‐hydroxybutan‐2‐yl)amino]propoxy}‐9H‐xanthen‐9‐one exerted activity in rats, p.o. 2 and 4 h after administration, respectively. Metabolic stability of the compounds was evaluated using rat microsomes, resulting in half‐life t1/2 136 and 108 min, respectively.