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Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties
Author(s) -
Waszkielewicz Anna M.,
Słoczyńska Karolina,
Pękala Elżbieta,
Żmudzki Paweł,
Siwek Agata,
Gryboś Anna,
Marona Henryk
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12842
Subject(s) - xanthone , chemistry , adme , anticonvulsant , stereochemistry , neurotoxicity , pharmacology , metabolism , biochemistry , toxicity , organic chemistry , biology , in vitro , neuroscience , epilepsy
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}‐9 H‐ xanthen‐9‐one and compound 12 : R,S ‐2‐{3‐[(1‐hydroxybutan‐2‐yl)amino]propoxy}‐9 H‐ 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 t 1/2 136 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.