Alzheimer’s disease (AD) is the most common form of dementia. While drugs that target several pathways underlying AD have been proposed, effective treatments remain to be discovered. BACE1, an enzyme associated with AD progression, is a promising target for developing anti-Alzheimer drugs. To find novel multifunctional anti-Alzheimer agents, we designed and synthesized a series of new substituted benzyl-1H-1,2,3-triazol-4-yl-N-cyclohexylimidazo[1,2-a]pyridin-3-amine. The in vitro screening results revealed that most of the compounds exhibited moderate to potent BACE1 and BuChE inhibitory and antioxidant activities. Compounds 7f and 7g, bearing dichloro (2,3-Cl₂ and 3,4-Cl₂) moieties on the benzyl pendant were selected as the most active compounds in our BACE1 inhibitory assay with respective IC₅₀ values of about 12 and 8.9 μM. In addition, compounds 7g and 7h (4-bromo derivative) showed the highest BuChE inhibitory activity with IC₅₀ of 3.2 and 2.5 µM, respectively. Compound 7g also possessed antioxidant activity with an IC₅₀ value of 10.2 μM and metal chelation potential. Moreover, docking studies were performed to investigate the possible mechanism of inhibition. Taken together, we demonstrate that N-cyclohexylimidazo[1,2-a]pyridine containing triazole motif derivatives deserve further investigation for anti-Alzheimer drug development.

阿尔茨海默氏病（AD）是痴呆症的最常见形式。虽然已经提出了针对AD的几种途径的药物，但是仍然需要发现有效的治疗方法。BACE1是一种与AD进展相关的酶，是开发抗阿尔茨海默病药物的有希望的靶标。为了找到新型的多功能抗阿尔茨海默病药物，我们设计并合成了一系列新的取代的苄基-1 H -1,2,3-三唑-4-基-N-环己基咪唑并[1,2- a ]吡啶-3-胺。的体外筛选结果表明，大多数化合物表现出中度至有效的BACE1和BuChE的抑制和抗氧化活性。化合物7f和7g，带有二氯（2,3-Cl ₂在我们的BACE1抑制试验中，苄基侧基上的3,4-Cl ₂）部分被选为活性最高的化合物，其IC ₅₀值分别约为12和8.9μM。此外，化合物7g和7h（4-溴衍生物）显示出最高的BuChE抑制活性，IC _50分别为3.2和2.5 µM。化合物7g还具有抗氧化活性，IC ₅₀值为10.2μM，具有金属螯合电位。此外，进行了对接研究以研究抑制的可能机制。两者合计，我们证明N -cyclohexylimidazo [1,2- a含[]吡啶的三唑基序衍生物值得进一步研究用于抗阿兹海默症药物的开发。