Synthesis of 8-substituted-4-(2/4-substituted phenyl)-2H-[1,3,5]triazino[2, 1-b][1,3]benzothiazole-2-thiones and their anticonvulsant, anti-nociceptive, and toxicity evaluation in mice

Abstract

A number of new 8-substituted-4-(2/4-substituted phenyl)-2H-[1,3,5] triazino[2,1-b][1,3]benzothiazole-2-thiones (4a-t) were synthesized and evaluated for their anticonvulsant, anti-nociceptive, hepatotoxic, and neurotoxic properties. The titled compounds (4a-t) were obtained by cyclization of N-[6-substituted-1,3-benzothiazol-2-yl)amino]carbonothioyl-2/4-substituted benzamides (3a-t) by refluxing in n-butanol. All the newly synthesized compounds were screened for their anticonvulsant activity in a mouse seizure model and were compared with the standard drug phenytoin. Compounds 4a, 4c, 4f, and 4l showed complete protection after time periods of 0.5h and 4h. Some of the selected compounds were evaluated for their neurotoxic and hepatotoxic effects, and none of these showed any sign of neurotoxicity or hepatotoxicity. Compounds 4a-t were also evaluated for their anti-nociceptive activity by a thermal stimulus technique using diclofenac as standard. Compounds 4o, 4q, and 4t displayed highly potent analgesic activity with p<0.01. © 2009 Informa UK Ltd.