Fluorinated piperidine acetic acids as gamma-secretase modulators.
Bioorg Med Chem Lett
; 20(2): 755-8, 2010 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-20005099
ABSTRACT
We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor. Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of Abeta42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250mg/kg per day, AUC(0-24)=2100microMh) did not exhibit Notch-related effects.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Piperidinas
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Secretasas de la Proteína Precursora del Amiloide
/
Flúor
/
Acetatos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos