N-(3-(2-amino-6,6-difluoro-4,4a,5,6,7,7a-hexahydro-cyclopenta[e][1,3]oxazin-4-yl)-phenyl)-amides as BACE1 inhibitors: a patent evaluation of WO2013041499.
Expert Opin Ther Pat
; 24(2): 239-42, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24219148
ABSTRACT
A new series of oxazin amides have been synthesized from isoxazoles using a reaction to increase the heterocyclic ring size and were evaluated as BACE1 inhibitors. The innovative compounds were able to diminish amyloid-ß peptide concentration in cell and proved to be selective toward peptidases from the same family. Further studies on the toxicity of this series showed that these new molecules were not recognized by P-glycoprotein and that they were unsusceptible to rapid metabolization by cytochrome P450 or glutathione conjugation. These results indicate that such compounds could be useful in developing drugs to fight Alzheimer's disease and that this novel oxazin scaffold should be considered as a starting point to tackle this pathology.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxazinas
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Inibidores de Proteases
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Ácido Aspártico Endopeptidases
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
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Amidas
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article