Difluorophenylglycinols as new modulators of proteolytic processing of amyloid precursor proteins.
Arch Pharm (Weinheim)
; 347(3): 161-73, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24339192
ABSTRACT
Synthesis and evaluation of difluorophenylglycinols as new modulators of proteolytic processing of the amyloid-ß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Precursor de Proteína beta-Amiloide
/
Etanolaminas
/
Secretases da Proteína Precursora do Amiloide
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article