%0 Journal Article
%T Design, Synthesis, and Biological Evaluation of 1-Benzylamino-2-hydroxyalkyl Derivatives as New Potential Disease-Modifying Multifunctional Anti-Alzheimer¡¯s Agents
%J -
%D 2018
%R https://doi.org/10.1021/acschemneuro.7b00461
%X The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer¡¯s disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, ¦Â-secretase, ¦Â-amyloid, and tau protein aggregation, all related to mechanisms which underpin Alzheimer¡¯s disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets, inhibition of ¦Â-secretase (IC50 hBACE-1 = 41.60 ¦ÌM), inhibition of amyloid ¦Â aggregation (IC50 A¦Â = 3.09 ¦ÌM), inhibition of tau aggregation (55% at 10 ¦ÌM); as well as against symptomatic targets, butyrylcholinesterase inhibition (IC50 hBuChE = 7.22 ¦ÌM). It might represent an encouraging starting point for development of multifunctional disease-modifying anti-Alzheimer¡¯s agents
%U https://pubs.acs.org/doi/10.1021/acschemneuro.7b00461