62992-68-1Relevant articles and documents
Design, synthesis, and evaluation of acetylcholinesterase and butyrylcholinesterase dual-target inhibitors against Alzheimer’s diseases
Guo, Yan,Yang, Hongyu,Huang, Zhongwei,Tian, Sen,Li, Qihang,Du, Chenxi,Chen, Tingkai,Liu, Yang,Sun, Haopeng,Liu, Zongliang
, (2020/02/11)
A series of novel compounds 6a–h, 8i–1, 10s–v, and 16a–d were synthesized and evaluated, together with the known analogs 11a–f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 μM) and BChE (eqBChE IC50 = 0.28 μM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer’s disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD.
Benzylpiperidine-benzimidazole derivative or pharmaceutically acceptable salt thereof, and preparation method and application thereof
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Paragraph 0049; 0055; 0066-0067, (2020/02/29)
The invention discloses a benzylpiperidine-benzimidazole derivative with a structure as shown in a general formula (I) or a pharmaceutically acceptable salt thereof, and a preparation method and application thereof. The derivative disclosed by the invention has good cholinesterase inhibition activity, can be used for preparing cholinesterase inhibitors, and is of important significance to treatment of neurodegenerative diseases.
Highly potent and selective aryl-1,2,3-triazolyl benzylpiperidine inhibitors toward butyrylcholinesterase in Alzheimer's disease
de Andrade, Peterson,Mantoani, Susimaire P.,Gon?alves Nunes, Paulo Sérgio,Magadán, Carlos Roca,Pérez, Concepción,Xavier, Danilo Jord?o,Hojo, Elza Tiemi Sakamoto,Campillo, Nuria E.,Martínez, Ana,Carvalho, Ivone
, p. 931 - 943 (2019/02/14)
Acetylcholinesterase (AChE) is the key enzyme targeted in Alzheimer's disease (AD) therapy, nevertheless butyrylcholinesterase (BuChE) has been drawing attention due to its role in the disease progression. Thus, we aimed to synthesize novel cholinesterases inhibitors considering structural differences in their peripheral site, exploiting a moiety replacement approach based on the potent and selective hAChE drug donepezil. Hence, two small series of N-benzylpiperidine based compounds have successfully been synthesized as novel potent and selective hBuChE inhibitors. The most promising compounds (9 and 11) were not cytotoxic and their kinetic study accounted for dual binding site mode of interaction, which is in agreement with further docking and molecular dynamics studies. Therefore, this study demonstrates how our strategy enabled the discovery of novel promising and privileged structures. Remarkably, compound 11 proved to be one of the most potent (0.17 nM) and selective (>58,000-fold) hBuChE inhibitor ever reported.
