The intricate and multifactorial nature of Alzheimer's disease (AD) requires the development of compounds able to hit different pathophysiological targets, such as cholinergic dysfunction, deposits of amyloid beta (Aβ) peptide and metal dyshomeostasis. In order to continue the search for new anti-AD drugs, a design strategy was once more followed based on repositioning donepezil (DNP) drug, by ortho-attaching a benzylpiperidine mimetic of DNP moiety to a hydroxyphenyl-benzimidazole (BIM) chelating unit (compound 1). Herein, compound 1 and a positional isomer 2 are compared in terms of their potential multiple properties: both present good acetylcholinesterase (AChE) inhibition (low μmolar range) and are moderate/good inhibitors of Aβ self- and Cu-mediated aggregation, the inhibition process being mainly due to ligand intercalation between the β-sheets of the fibrils; compound 1 has a higher chelating capacity towards Cu²⁺ and Zn²⁺ (pCu = 14.3, pZn = 6.4, pH 7.4, C_L/C_M = 10, C_M = 10⁻⁶ M) than 2 (pCu = 10.7, pZn = 6.3), attributed to its ability to establish a tridentate (N,O,O) coordination to the metal ion. Both compounds are eligible as drug candidates for oral administration but compound 1 shows improved neuroprotective role by completely preventing Aβ-induced cell toxicity.

阿尔茨海默氏病（AD）的复杂和多因素性质要求能够击中不同的病理生理的目标，如胆碱能功能障碍，淀粉样蛋白β（A存款化合物的开发β）肽和金属dyshomeostasis。为了继续寻找新的抗AD药物，在重新定位多奈哌齐（DNP）药物的基础上，通过将DNP部分的苄基哌啶模拟物与羟基苯基-苯并咪唑（BIM）螯合单元邻位连接，再次遵循了一种设计策略（化合物1）。在此，化合物1和位置异构体2在它们的潜在的多个性能方面相比：两者都存在良好乙酰胆碱酯酶（AChE）抑制（低微摩尔范围），并且A的中等/良好抑制剂β自和Cu介导的聚集，抑制过程为主要是由于配体之间插原纤维的β-折叠；化合物1对Cu ²⁺和Zn ^2+的螯合能力（pCu = 14.3，pZn = 6.4，pH 7.4，C _L / C _M  = 10，C _M  = 10 ^-6  M）具有比2（pCu = 10.7， pZn = 6.3），归因于其建立三齿齿的能力（N，O，O）与金属离子配位。两种化合物有资格作为候选药物用于口服给药，但化合物1个显示出改进的通过完全防止神经保护作用β诱导的细胞毒性。