76876-70-5Relevant articles and documents
Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine N-benzylpiperidine fragments
Zhou, Yeheng,Sun, Wei,Peng, Jiale,Yan, Hui,Zhang, Li,Liu, Xingyong,Zuo, Zhili
, (2019/10/08)
Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62 nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer's disease based on the fusion of donepezil and curcumin
Yan, Jun,Hu, Jinhui,Liu, Anqiu,He, Lin,Li, Xingshu,Wei, Hui
, p. 2946 - 2955 (2017/05/25)
By fusing donepezil and curcumin, a novel series of compounds were obtained as multitarget-directed ligands against Alzheimer's disease. Among them, compound 11b displayed potent acetylcholinesterase (AChE) inhibition (IC50?=?187?nM) and the highest BuChE/AChE selectivity (66.3). Compound 11b also inhibited 45.3% Aβ1–42 self-aggregation at 20?μM and displayed remarkable antioxidant effects. The metal-chelating property of compound 11b was elucidated by determining the 1:1 stoichiometry for the 11b–Cu(II) complex. The excellent blood–brain barrier permeability of 11b also indicated the potential for the compound to penetrate the central nervous system.
Synthesis of some new 4-substituted N-benzyl-piperidines
Doernyei, Gabor,Incze, Maria,Moldvai, Istvan,Szantay, Csaba
, p. 2329 - 2338 (2007/10/03)
Via Knoevenagel condensation of N-benzyl-4-piperidone with malononitrile some new 4-substituted N-benzyl-piperidines have been prepared. By means of these transformations an economic and large-scale synthesis of biologically important intermediate N-benzyl-piperidine-4-ethanol has been elaborated.
