Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole.
A series of 6-substituted-[3-substituted-prop-2-eneamido]benzothiazole 9-32 and 6-substituted-2-[(1-acetyl-5-substituted)-2-pyrazolin-3-yl]aminobenzothiazole 33-56 were synthesized using appropriate synthetic route and evaluated experimentally against maximal electroshock test. Selected compounds were evaluated for neurotoxicity, hepatotoxicity and behavioral study. The most active compound, 6-methyl-2-[(1-acetyl-5-(4-chlorophenyl))-2-pyrazolin-3-yl]aminobenzothiazole 52 exhibited an ED50 of 25.49 micromol/kg, TD50 of 123.87 micromol/kg and high protective index (PI) of 4.86 compared to standard drug phenytoin. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power (r2=0.9220, q2=0.8144) was achieved. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may aids in the design of potent aminobenzothiazole derivatives as anticonvulsant agents.
Department of Medicinal Chemistry, Sharad Pawar College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 441 110, Maharashtra, India. nikhilamnerkar@gmail.com
Nikhil D
ND
Amnerkar
Kishore P
KP
Bhusari
D000410:Alanine Transaminase / Q000097:blood; D000475:Alkenes / Q000737:chemistry*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D011720:Pyrazoles / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D012984:Software
D000475:Alkenes; D000927:Anticonvulsants; D052160:Benzothiazoles; D011720:Pyrazoles; C523775:aminobenzothiazole compound; C013658:propylene; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase