Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors.
Bioorg Med Chem Lett
; 21(7): 1942-7, 2011 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-21388807
ABSTRACT
This Letter describes the de novo design of non-peptidic hydroxyethylamine (HEA) inhibitors of BACE-1 by elimination of P-gp contributing amide attachments. The predicted binding mode of the novel cyclic sulfone HEA core template was confirmed in a X-ray co-crystal structure. Inhibitors of sub-micromolar potency with an improved property profile over historic HEA inhibitors resulting in improved brain penetration are described.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzilaminas
/
Ácido Aspártico Endopeptidases
/
Óxidos S-Cíclicos
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Inibidores Enzimáticos
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Secretases da Proteína Precursora do Amiloide
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2011
Tipo de documento:
Article