Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 43, Issue 1, Pages 135-141Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2007.02.004
Keywords
4(3H)-quinazolinones; MES; subcutaneous pentylenetetrazole induced seizure
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A series of novel 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones were synthesized and evaluated for anticonvulsant, sedative-hypnotic and CNS depressant activities. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2-styrylquinazolin-4(3H)-one derivatives were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. Out of eighteen compounds only 4a, 4d, 4e, 4j and 4k showed anticonvulsant activity in one or more test models. All except 4e and 4f exhibited significant sedative-hypnotic activity via actophotometer screen. CNS depressant activity screened with the help of the forced swim pool method resulted into some potent compounds. From the experimental observation it can be concluded that synthesized compounds exhibited relatively better sedative-hypnotic and CNS depressant activities. (C) 2007 Elsevier Masson SAS. All rights reserved.
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