Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics.
Bioorg Med Chem Lett
; 19(13): 3674-8, 2009 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-19406640
ABSTRACT
Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improved pharmacokinetic profiles. In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Ácido Aspártico Endopeptidases
/
Etilaminas
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido