Department of Chemistry, Lehigh University, Bethlehem, PA 18015, USA.
Bioorg Med Chem Lett. 2010 May 1;20(9):2987-90. doi: 10.1016/j.bmcl.2010.02.102. Epub 2010 Mar 3.
The design and study of two classes of noncompetitive acetylcholinesterase inhibitors (AChEIs) which also function as NSAID prodrugs are reported. The most potent AChEIs disclosed contain an aromatic alkyl-aryl linker between an NSAID and a lipophilic choline mimic and they inhibit acetylcholinesterase (AChE) in the submicromolar range. These agents have the therapeutic potential to dually target inflammation by releasing an NSAID in vivo and activating the cholinergic anti-inflammatory pathway via cholinergic up-regulation.
报告了两类非竞争性乙酰胆碱酯酶抑制剂（AChEIs）的设计和研究，它们也可作为 NSAID 前药。所揭示的最有效的 AChEIs 在 NSAID 和亲脂性胆碱模拟物之间包含芳基烷基-芳基连接体，并且它们在亚微摩尔范围内抑制乙酰胆碱酯酶（AChE）。这些药物具有通过体内释放 NSAID 和通过胆碱能上调激活胆碱能抗炎途径来双重靶向炎症的治疗潜力。
