Pudlo Marc, Luzet Vincent, Ismaïli Lhassane, Tomassoli Isabelle, Iutzeler Anne, Refouvelet Bernard
Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France.
Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France.
Bioorg Med Chem. 2014 Apr 15;22(8):2496-507. doi: 10.1016/j.bmc.2014.02.046. Epub 2014 Mar 7.
Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining quinolinecarboxamide to a benzylpiperidine moiety are described. Then, a series of hybrids have been developed by introducing radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds show effective AchE inhibitions, high selectivities over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of quinolone derivatives to serve in the design of N-benzylpiperidine linked multipotent molecules for the treatment of Alzheimer Disease has been established.
本文描述了通过将喹啉甲酰胺与苄基哌啶部分相结合来设计、合成和评估新型乙酰胆碱酯酶抑制剂的过程。然后,通过引入自由基清除剂开发了一系列杂化物。进行了分子建模并讨论了构效关系。在该系列中,大多数强效化合物显示出有效的乙酰胆碱酯酶抑制作用、对丁酰胆碱酯酶的高选择性和高自由基清除活性。基于这项工作,已确定喹诺酮衍生物在设计用于治疗阿尔茨海默病的N-苄基哌啶连接的多效性分子方面的能力。