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Chem Biol Drug Des. 2017 Mar;89(3):339-352. doi: 10.1111/cbdd.12842. Epub 2016 Sep 28.

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

Author information

1
Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
2
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
3
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
4
Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.

Abstract

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.

KEYWORDS:

MES ; 9H-xanthen-9-one; aminoalkanols; metabolic stability; rat microsomes; seizures; status epilepticus; xanthone

PMID:
27543433
DOI:
10.1111/cbdd.12842
[Indexed for MEDLINE]

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