Beside acetylcholinesterase, butyrylcholinesterase could be considered as a putative target of interest for the symptomatic treatment of Alzheimer’s disease (AD). As a result of complexity of AD, no molecule has been approved since 2002. Idalopirdine, a 5-HT₆ receptors antagonist, did not show its effectiveness in clinical trial despite its evaluation as adjunct to cholinesterase inhibitors. Pleiotropic molecules, known as multitarget directed ligands (MTDLs) are currently developed to tackle the multifactorial origin of AD. In this context, we have developed a pleiotropic carbamate 7, that behaves as a covalent inhibitor of BuChE (IC₅₀ = 0.97 μM). The latter will deliver after hydrolysis, compound 6, a potent 5-HT₆ receptors antagonist (K_i = 11.4 nM) related to idalopirdine. In silico and in vitro evaluation proving our concept were performed completed with first in vivo results that demonstrate great promise in restoring working memory.

除乙酰胆碱酯酶外，丁酰胆碱酯酶也可被视为对症治疗阿尔茨海默氏病（AD）的假定靶标。作为AD的复杂性的结果，没有分子已被批准自2002年以来Idalopirdine，一个5-HT ₆受体拮抗剂，没有显示出其在临床试验中效力，尽管其作为辅助胆碱酯酶抑制剂的评价。多向性分子，称为多靶标定向配体（MTDL），目前正在开发中，以解决AD的多因素起源。在这种情况下，我们开发了一种多效性氨基甲酸酯7，可作为BuChE的共价抑制剂（IC ₅₀  = 0.97μM）。水解，化合物后后者将提供6，一种有效的5-HT ₆ 与伊洛吡定有关的受体拮抗剂（K _i = 11.4 nM）。通过计算机和体外评估证明了我们的概念已完成，并获得了首次体内结果，这些结果显示出恢复工作记忆的巨大希望。