Discovery of potent iminoheterocycle BACE1 inhibitors.
Bioorg Med Chem Lett
; 24(23): 5455-9, 2014 Dec 01.
Article
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| MEDLINE
| ID: mdl-25455483
ABSTRACT
The synthesis of a series of iminoheterocycles and their structure-activity relationships (SAR) as inhibitors of the aspartyl protease BACE1 will be detailed. An effort to access the S3 subsite directly from the S1 subsite initially yielded compounds with sub-micromolar potency. A subset of compounds from this effort unexpectedly occupied a different binding site and displayed excellent BACE1 affinities. Select compounds from this subset acutely lowered Aß40 levels upon subcutaneous and oral administration to rats.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ácido Aspártico Endopeptidasas
/
Secretasas de la Proteína Precursora del Amiloide
/
Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article