Macrocyclic BACE inhibitors: Optimization of a micromolar hit to nanomolar leads.
Bioorg Med Chem Lett
; 20(10): 3158-60, 2010 May 15.
Article
en En
| MEDLINE
| ID: mdl-20399652
ABSTRACT
We have identified macrocyclic inhibitors of the aspartic protease BACE, implicated in the etiology of Alzheimer's disease. An X-ray structure of screening hit 1 in the BACE active site revealed a hairpin conformation suggesting that constrained macrocyclic derivatives may also bind there. Several of the analogs we prepared were >100x more potent than 1, such as 7 (5 nM K(i)).
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteasas
/
Quinazolinas
/
Ácido Aspártico Endopeptidasas
/
Compuestos Macrocíclicos
/
Secretasas de la Proteína Precursora del Amiloide
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos