Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole templates.
Bioorg Med Chem Lett
; 22(21): 6721-7, 2012 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-23010268
ABSTRACT
A set of low molecular weight compounds containing a hydroxyethylamine (HEA) core structure with different prime side alkyl substituted 4,5,6,7-tetrahydrobenzazoles and one 4,5,6,7-tetrahydropyridinoazole was synthesized. Striking differences were observed on potencies in the BACE-1 enzymatic and cellular assays depending on the nature of the heteroatoms in the bicyclic ring, from the low active compound 4 to inhibitor 6, displaying BACE-1 IC(50) values of 44 nM (enzyme assay) and 65 nM (cell-based assay).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Azóis
/
Benzoxazóis
/
Desenho de Fármacos
/
Ácido Aspártico Endopeptidases
/
Inibidores Enzimáticos
/
Etilaminas
/
Secretases da Proteína Precursora do Amiloide
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2012
Tipo de documento:
Article