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-4 h 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 is 5-[2'-amino-5'-[3"-aminomethylene-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.
Medicinal Chemistry Division, Department of Pharmacology, L.L.R.M. Medical College, Meerut-250004 (U.P.), India.
Archana
V K
VK
Srivastava
Ashok
A
Kumar
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D016292:Procedural Sedation; D005106:Exploratory Behavior / Q000187:drug effects; D006990:Hypnosis; D009043:Motor Activity / Q000187:drug effects; D011799:Quinazolines; D051381:Rats; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control; D012890:Sleep / Q000187:drug effects; D013858:Thiobarbiturates / Q000138:chemical synthesis* / Q000494:pharmacology*
D000927:Anticonvulsants; D011799:Quinazolines; D013858:Thiobarbiturates; C029684:thiobarbituric acid