Design and synthesis of some new derivatives of 3H-quinazolin-4-one with promising anticonvulsant activity.
A new series of 3-substituted (methyl, ethyl or phenyl)-3H-quinazolin-4-one derivatives (4a-l) were synthesized through condensation reaction of their potassium salts (3a-l) with methyl, ethyl and phenylisocyanate. The newly synthesized derivatives (4a-l) were evaluated for anticonvulsant activity. It was found that these compounds showed the highest anticonvulsant activity at low doses (50-100 mg kg(-1)), whereas at doses over 100 mg kg(-1) they showed a stimulant effect on the central nervous system that even potentiated the effect of the convulsive agent, pentylenetetrazole, in mice. A series of halogenated derivatives, 3-methyl, 3-ethyl and 3-phenyl-6-mono and 6,8-disubstituted-3H-quinazolin-4-one derivatives (4m-z) was also synthesized and evaluated for anticonvulsant activity. Reduced anticonvulsant activity was recorded. Phenobarbitone sodium was used as a reference drug.
El-Helby
Abdel Ghany Aly
AG
Department of Pharmaceutical Chemistry, Faculty of Pharmacy Al-Azhar University Nasr City, Cairo, Egypt. menazmd@hotmail.com
Wahab
Mohammed Hemeda Abdel
MH
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D000927:Anticonvulsants; D003292:Convulsants; D007202:Indicators and Reagents; D011799:Quinazolines; D010433:Pentylenetetrazole; D010634:Phenobarbital