Synthesis of some newer derivatives of substituted quinazolinonyl-2-oxo/thiobarbituric acid as potent anticonvulsant agents

5-{1'-[3"-Aminoacetyl-2"-methyl-6",8"-dihalosubstitutedquinazolin-4"(3"H)-onyl]-thiosemicarbazido}-2-oxo/thiobarbituric acids 3a-3h and 5-{2'-amino-5'-[3"-aminomethylene-2"-methyl-6",8"-dihalosubstitutedquinazolin-4"(3"H)-onyl]-1',3,4'-thiadiazol-2'-yl}-2-oxo/thiobarbituric acid 5a-5h were prepared by incorporating 1-[3'-aminoacetyl-2'-methyl-6",8"-dihalosubstituted-quinazolin-4'(3'H)-onyl]-thiosemicarbazides 2a-2d and 2-amino-5-[3'-aminomethylene-2'-methyl-6',8'-dihalosubstituted-quinazolin-4'(3'H)-onyl]-1,3,4-thiadiazoles 4a-4h respectively at 5(th) position of 2-oxo/thiobarbituric acids' (via Mannich reaction). All the newly synthesized compounds were screened for their anti-convulsant activity in MES and PTZ models and were compared with standard drugs phenytoin sodium and sodium valproate. Interestingly, these compounds were found to be devoid of sedative and hypnotic activities when tested. Out of the compounds studied, the most active compound 5h, that is5-{2'-amino-5'-[3"-amino-methylene-2"-methyl-6",8"-dibromoquinazolin-4"(3"H)-onyl]-1',3',4'-thiadiazol-2'-yl}-2-thiobarbituric acid showed activity (90%) more potent than the standard drug. (C) 2003 Elsevier Ltd. All rights reserved.