Butyrylcholinesterase (BuChE) inhibitors have become interesting target for treatment of Alzheimer's disease (AD). A series of dual binding site BuChE inhibitors were designed and synthesized based on 2,3,4,9-tetrahydro-1H-carbazole attached benzyl pyridine moieties. In-vitro assay revealed that all of the designed compounds were selective and potent BuChE inhibitors. The most potent BuChE inhibitor was compound 6i (IC₅₀ = 0.088 ± 0.0009 μM) with the mixed-type inhibition. Docking study revealed that 6i is a dual binding site BuChE inhibitor. Also, Pharmacokinetic properties for 6i were accurate to Lipinski's rule. In addition, compound 6i demonstrated neuroprotective and β-secretase (BACE1) inhibition activities. This compound could also inhibit AChE-induced and self-induced Aβ peptide aggregation at concentration of 100 μM and 10 μM respectively. Generally, the results are presented as new potent selective BuChE inhibitors with a therapeutic potential for the treatment of AD.

丁酰胆碱酯酶（BuChE）抑制剂已成为治疗阿尔茨海默氏病（AD）的有趣靶标。基于2,3,4,9-四氢-1H-咔唑连接的苄基吡啶部分，设计和合成了一系列双结合位点BuChE抑制剂。体外测定表明，所有设计的化合物均为选择性和有效的BuChE抑制剂。最有效的BuChE抑制剂是化合物6i（IC ₅₀ = 0.088±0.0009μM），具有混合型抑制作用。对接研究表明6i是BuChE双重结合位点抑制剂。同样，6i的药代动力学特性与Lipinski的定律是准确的。此外，化合物6i表现出神经保护和β-分泌酶（BACE1）抑制活性。该化合物还可以分别在100μM和10μM的浓度下抑制AChE诱导的Aβ肽和自身诱导的Aβ肽聚集。通常，结果显示为具有治疗AD潜在治疗潜力的新型有效BuChE抑制剂。