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.
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 0.5 h and 4 h. 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.
Siddiqui
Nadeem
N
Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India. nadeems_03@yahoo.co.in
Rana
Arpana
A
Khan
Suroor A
SA
Haque
Syed Ehtaishamul
SE
Alam
M Shamsher
MS
Ahsan
Waquar
W
Ahmed
Sharique
S
D000700:Analgesics / Q000138:chemical synthesis* / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000473:pathology; D010672:Phenytoin / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017550:Spectroscopy, Fourier Transform Infrared; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity*; D013871:Thiones / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity*; D013997:Time Factors
D000700:Analgesics; D000927:Anticonvulsants; D013830:Thiadiazoles; D013871:Thiones; D010672:Phenytoin