Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation.
Bioorg Med Chem Lett
; 17(6): 1788-92, 2007 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-17257835
ABSTRACT
A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Ácido Aspártico Endopeptidases
/
Niacinamida
/
Inibidores Enzimáticos
/
Secretases da Proteína Precursora do Amiloide
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article