Synthesis and anticonvulsant activity of acetylenic quinazolinone derivatives.
Acetylenic derivatives of quinazolinones and quinazolinediones were synthesized and evaluated for their anticonvulsant activity. Most compounds displayed seizure-antagonizing activity in the maximal electroschock test (MES test) in most cases associated with little or no acute neurotoxicity determined in the rotorod test. Only three compounds exhibited significant activity in the seizure threshold test with subcutaneous pentylenetetrazole (scMet test). Based on the ED50 in the MES test, 1,3-bis-(prop-2-ynyl)-quinazoline-2,4-(1H,3H)-dione(9a) was about ten-fold less active than phenytoin or carbamazepine but about as active as mesuximide.
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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Benin, Nigeria.
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D000114:Acetylene / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology
D000927:Anticonvulsants; D007659:Ketones; D011799:Quinazolines; D000114:Acetylene