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Difluorophenylglycinols as New Modulators of Proteolytic Processing of Amyloid Precursor Proteins
Author(s) -
Chen ChiaYu,
Liao YungFeng,
Chang MingYun,
Hu MingKuan
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300283
Subject(s) - chemistry , enantiomer , mapk/erk pathway , amyloid precursor protein secretase , amyloid (mycology) , amyloid precursor protein , biochemistry , stereochemistry , signal transduction , alzheimer's disease , medicine , inorganic chemistry , disease , pathology
Synthesis and evaluation of difluorophenylglycinols as new modulators of proteolytic processing of the amyloid‐β precursor proteins for Alzheimer's therapies were described. A range of N ‐substituted ( R )‐ and ( S )‐difluorophenylglycinols, structured on the amino alcohol framework, were explored by incorporating the arylsulfonyl moieties and various N ‐substituents. Evans' chiral auxiliary strategy was employed for the asymmetric synthesis of these enantiomeric difluorophenylglycinols. Compounds with effects on the γ‐secretase inhibition and ERK‐mediated signaling pathways were evaluated on cell‐based assays. Among them, N ‐cyclopropylmethyl derivatives R ‐ 12c and R ‐ 13c showed modest γ‐secretase inhibition as well as ERK‐dependent activation.