Department of Medicinal Chemistry, Sharad Pawar College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 441 110, Maharashtra, India.
Eur J Med Chem. 2010 Jan;45(1):149-59. doi: 10.1016/j.ejmech.2009.09.037. Epub 2009 Sep 30.
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.
一系列 6-取代-[3-取代-丙烯酰胺基]苯并噻唑 9-32 和 6-取代-2-[(1-乙酰基-5-取代基)-2-吡唑啉-3-基]氨基苯并噻唑 33-56 通过适当的合成路线合成，并在最大电休克试验中进行了实验评估。选择的化合物进行了神经毒性、肝毒性和行为研究。最活跃的化合物 6-甲基-2-[(1-乙酰基-5-(4-氯苯基))-2-吡唑啉-3-基]氨基苯并噻唑 52 表现出 ED50 为 25.49 μmol/kg、TD50 为 123.87 μmol/kg 和高保护指数 (PI) 为 4.86，与标准药物苯妥英钠相比。通过 PHASE 程序进行了 3D-QSAR 分析，得到了一个具有良好预测能力的统计可靠模型（r2=0.9220，q2=0.8144）。3D-QSAR 图说明了这些化合物的构效关系的见解，这可能有助于设计有效的苯并噻唑衍生物作为抗惊厥药物。
