3,3-Difluoro-3,4,5,6-tetrahydropyridin-2-amines: Potent and permeable BACE-1 inhibitors.
Bioorg Med Chem Lett
; 30(8): 126999, 2020 04 15.
Article
en En
| MEDLINE
| ID: mdl-32089426
ABSTRACT
Since its discovery in 1999, BACE-1, a membrane anchored aspartyl protease expressed primarily in the CNS, has been the target of numerous medicinal chemistry research programs. These efforts have produced highly potent inhibitors with nanomolar affinity and ever-increasing structural complexity. However, only a handful of these molecules have been able to combine in vitro potency with CNS permeability and progressed to the clinic. Herein, we describe a set of novel piperidine-based inhibitors. This investigation culminated with the identification of 43, a highly potent (IC50 1.5 nM), permeable BACE-1 inhibitor with a low susceptibility to Pgp-mediatedefflux.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteasas
/
Ácido Aspártico Endopeptidasas
/
Secretasas de la Proteína Precursora del Amiloide
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article