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.
Amnerkar
Nikhil D
ND
Department of Medicinal Chemistry, Sharad Pawar College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 441 110, Maharashtra, India. nikhilamnerkar@gmail.com
Bhusari
Kishore P
KP
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