A series of hybrids of benzimidazole and 1,3,5-triazine were designed and synthesized and evaluated as multi-target agents for the treatment of Alzheimer's disease. 24 compounds were designed, synthesized and identified by NMR, IR, HRMS and single-crystal X-ray diffraction studies. The compound 6c had the crystal system of orthorhombic and the space group of P2₁2₁2₁. The cholinesterase inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. Most 1,3,5-triazine-benzimidazole hybrids showed potent acetylcholinesterase-inhibition activities and weak butyrylcholinesterase inhibitory activities. Compound 9f possessed the best acetylcholinesterase inhibitory activity with the IC₅₀ of 0.044 µM, which is better than donepezil (0.052 µM). Molecular docking and molecular dynamics simulations demonstrated that there is a stable interaction between compound 9f and acetylcholinesterase. Simultaneously, experiments have also proved that compound 9f has good metal chelating properties. ADMET in silico prediction results suggest the compound can pass through the blood-brain barrier well and have good drug similarity. So, compound 9f could be a multi-target agent for the treatment of Alzheimer's disease.

设计和合成了一系列苯并咪唑和 1,3,5-三嗪的杂化物，并对其作为治疗阿尔茨海默病的多靶点药物进行了评估。通过 NMR、IR、HRMS 和单晶 X 射线衍射研究设计、合成和鉴定了 24 种化合物。化合物6c的晶系为斜方晶系，空间群为P2 ₁ 2 ₁ 2 ₁。合成化合物的胆碱酯酶抑制活性使用比色埃尔曼法测量。大多数1,3,5-三嗪-苯并咪唑杂化物显示出有效的乙酰胆碱酯酶抑制活性和较弱的丁酰胆碱酯酶抑制活性。化合物9f具有最佳的乙酰胆碱酯酶抑制活性，IC ₅₀为0.044 µM，优于多奈哌齐（0.052 µM）。分子对接和分子动力学模拟表明化合物9f和乙酰胆碱酯酶之间存在稳定的相互作用。同时，实验也证明化合物9f具有良好的金属螯合性能。ADMET in silico 预测结果表明该化合物能很好地通过血脑屏障，具有良好的药物相似性。因此，化合物9f可能是治疗阿尔茨海默病的多靶点药物。