388073-65-2Relevant academic research and scientific papers
Discovery of multifunctional anti-Alzheimer's agents with a unique mechanism of action including inhibition of the enzyme butyrylcholinesterase and γ-aminobutyric acid transporters
Pasieka, Anna,Panek, Dawid,Jończyk, Jakub,Godyń, Justyna,Sza?aj, Natalia,Latacz, Gniewomir,Tabor, Julia,Mezeiova, Eva,Chantegreil, Fabien,Dias, José,Knez, Damijan,Lu, Junfeng,Pi, Rongbiao,Korabecny, Jan,Brazzolotto, Xavier,Gobec, Stanislav,H?fner, Georg,Wanner, Klaus,Wi?ckowska, Anna,Malawska, Barbara
supporting information, (2021/04/12)
Looking for an effective anti-Alzheimer's agent is very challenging; however, a multifunctional ligand strategy may be a promising solution for the treatment of this complex disease. We herein present the design, synthesis and biological evaluation of novel hydroxyethylamine derivatives displaying unique, multiple properties that have not been previously reported. The original mechanism of action combines inhibitory activity against disease-modifying targets: β-secretase enzyme (BACE1) and amyloid β (Aβ) aggregation, along with an effect on targets associated with symptom relief - inhibition of butyrylcholinesterase (BuChE) and γ-aminobutyric acid transporters (GATs). Among the obtained molecules, compound 36 exhibited the most balanced and broad activity profile (eeAChE IC50 = 2.86 μM; eqBuChE IC50 = 60 nM; hBuChE IC50 = 20 nM; hBACE1 IC50 = 5.9 μM; inhibition of Aβ aggregation = 57.9% at 10 μM; mGAT1 IC50 = 10.96 μM; and mGAT2 IC50 = 19.05 μM). Moreover, we also identified 31 as the most potent mGAT4 and hGAT3 inhibitor (IC50 = 5.01 μM and IC50 = 2.95 μM, respectively), with high selectivity over other subtypes. Compounds 36 and 31 represent new anti-Alzheimer agents that can ameliorate cognitive decline and modify the progress of disease.
NOVEL 9H-FLUORENE DERIVATIVES OR THEIR PHARMACEUTICALLY ACCEPTABLE SALTS
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Page/Page column 9-14, (2021/12/07)
A group of novel 9H-fluorcnc derivatives suitable for the preparation of active substances for the treatment of Alzheimer's disease, in particular as multifunctional inhibitors of the BuChE and BACE1 enzymes and beta-amyloid aggregation.
BETA-SECRETASE INHIBITING COMPOUNDS
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Page/Page column 60, (2009/04/25)
Disclosed are compounds represented by Formula (I) as defined in the specification, or pharmaceutically acceptable salts or isomers thereof, and a pharmaceutical composition for inhibiting beta-secretase activity comprising a therapeutically effective amount of the same.
