Synthesis of 3,4-dihydro-4-oxoquinazoline derivatives as potential anticonvulsants.
Twenty-three substituted 3,4-dihydro-4-oxoquinazolines or 3,4-dihydro-4-oxoazaquinazolines have been synthesized utilizing 2-amino-3-cyano-4,5-dimethylfuran and methyl acrylate as precursors for synthesis of the required substituted anthranilates. Six additional azaquinazolones were synthesized from 2-aminonicotinic or 3-aminopicolinic acid for comparison studies. All compounds were evaluated in mice with the maximal electroshock (MES) seizure and pentylenetetrazol (sc Met) seizure threshold tests for potential anticonvulsant activity and in the rotorod test to evaluate neurotoxicity. Nine of the twenty-nine compounds in the series demonstrated anticonvulsant action. The azaquinazolones were found to possess the most significant activity.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D011799:Quinazolines / Q000138:chemical synthesis* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D011799:Quinazolines; D010433:Pentylenetetrazole