New Benzo[d]thiazol-2-yl-aminoacetamides as Potential Anticonvulsants: Synthesis, Activity and Prediction of Molecular Properties

作者：Ali Ruhi; Siddiqui Nadeem^*

来源：Archiv der Pharmazie, 2015, 348(4): 254-265.

DOI：10.1002/ardp.201400466

• Anticonvulsant
• Benzothiazole
• Hepatotoxicity
• In vivo
• In silico
• Neurotoxicity

A series of N-(substituted-2-oxo-4-phenylazetidin-1-yl)-2-((6-substitutedbenzo[d]thiazol-2-yl)amino)acetamide derivatives were synthesized using pharmacophoric features with aromatic hydrophobic aryl ring (A), NHCO as hydrogen bonding domain, the nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). The synthesized molecules were initially screened for anticonvulsant activity using the maximal electroshock seizure (MES) test and the subcutaneous pentylenetetrazole test in albino mice. An acute neurotoxicity study on the synthesized molecules was also carried out using the rotarod test. The results of these tests revealed that two compounds, 5b and 5q, showed promising activity with ED50 values of 15.4 and 18.6mg/kg and protective indices of 20.7 and 34.9 in the MES test, respectively, which are found to be approximately fourfold higher than those of the standard drugs phenytoin (6.9) and carbamazepine (8.1). These molecules may act as lead of the designed scheme. The pharmacokinetic profiles of all the synthesized compounds were estimated using Molinspiration software. None of the compounds violated Lipinski's rule of five. The possible structure-activity relationship was discussed. In conclusion, this manuscript shows that the developed model has a highly prognostic power for the further investigation of better benzothiazole derivatives for future discovery and development.

• 出版日期2015-4