Synthesis of newer indolyl/phenothiazinyl substituted 2-oxo/thiobarbituric acid derivatives as potent anticonvulsant agents.
2-Amino-5-(heteroarylmethylene)-1,3,4-oxadiazoles/thiadiazoles 7-10 were synthesized by cyclisation of 1-(heteroarylacetyl)semicarbazides/thiosemicarbazides 3-6. 5-(2'-Heteroarylmethylene-5'-aminomethylene-1',3,'4'- oxadiazol-2'-yl/thiadiazol-2'-yl)-2-oxo/thiobarbituric acids 11-18 were synthesized by condensation of compounds 7-10 at the 5th position of 2-oxo/thiobarbituric acids. The newly synthesized compounds showed anticonvulsant activity ranging from 50-90% (seizures protection). Compound 18 (5-(2'-phenothiazinylmethylene-5'-aminomethylene-1',3',4'-thiadiazol-2'- yl)-2-thiobarbituric acid) showed maximum activity being more potent than the reference drug phenytoin sodium (CAS 630-93-3).
Archana
Medicinal Chemistry Division, Department of Pharmacology, Lala Lajpat Rai Memorial Medical College, Meerut, U.P., India.
Rani
Preeti
P
Bajaj
Kiran
K
Srivastava
Virendra Kishore
VK
Chandra
Ramesh
R
Kumar
Ashok
A
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005260:Female; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010640:Phenothiazines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000517:prevention & control; D013858:Thiobarbiturates / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
D000927:Anticonvulsants; D007202:Indicators and Reagents; D010640:Phenothiazines; D013858:Thiobarbiturates; D010672:Phenytoin