Verma Shweta, Kumar Surendra, Kumar Sushil
Faculty of Pharmacy, IFTM University, Moradabad-244001 (U.P.). India.
Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, Lucknow-226028 (U.P.). India.
Cent Nerv Syst Agents Med Chem. 2017;17(3):229-238. doi: 10.2174/1871524917666170321103951.
A series of new N-(2-benzoyl-4-chlorophenyl)-2-(4-(substituted phenyl) piperazin-1-yl) acetamides (3a-j) have been synthesized by the chloroacetylation of 2-amino-5- chlorbenzophenone which was further reacted with substituted phenylpiperazine.
The chemical structures of the compounds were confirmed on the basis of their TLC, IR, 1HNMR, 13CNMR and by elemental analysis. The physicochemical similarity of the target compounds with respect to standard drug diazepam was assessed by calculating from a set of physicochemical properties using software programs.
Molecular docking studies revealed that the target compounds correctly dock into the binding pocket of the GABAA receptor, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. The anxiolytic and skeletal muscle relaxant activity of the target compounds (3a-j) were evaluated in albino mice. Among them, compound 3h showed potent anxiolytic and skeletal muscle relaxant activity.
通过2-氨基-5-氯二苯甲酮的氯乙酰化反应合成了一系列新的N-(2-苯甲酰基-4-氯苯基)-2-(4-(取代苯基)哌嗪-1-基)乙酰胺(3a-j)，该产物再与取代苯基哌嗪反应。
通过TLC、IR、1HNMR、13CNMR以及元素分析确定了化合物的化学结构。使用软件程序从一组物理化学性质计算评估目标化合物与标准药物地西泮的物理化学相似性。
分子对接研究表明，目标化合物正确地对接至GABAA受体的结合口袋，同时预测它们的生物利用度/类药性是可接受的，但需要未来进一步优化。在白化小鼠中评估了目标化合物(3a-j)的抗焦虑和骨骼肌松弛活性。其中，化合物3h表现出强效的抗焦虑和骨骼肌松弛活性。
