Benzoxazin-4-ones as novel, easily accessible inhibitors for rhomboid proteases.
Bioorg Med Chem Lett
; 28(8): 1423-1427, 2018 05 01.
Article
en En
| MEDLINE
| ID: mdl-29506958
ABSTRACT
Rhomboid proteases form one of the most widespread intramembrane protease families. They have been implicated in variety of human diseases. The currently reported rhomboid inhibitors display some selectivity, but their construction involves multistep synthesis protocols. Here, we report benzoxazin-4-ones as novel inhibitors of rhomboid proteases with a covalent, but slow reversible inhibition mechanism. Benzoxazin-4-ones can be synthesized from anthranilic acid derivatives in a one-step synthesis, making them easily accessible. We demonstrate that an alkoxy substituent at the 2-position is crucial for potency and results in low micromolar inhibitors of rhomboid proteases. Hence, we expect that these compounds will allow rapid synthesis and optimization of inhibitors of rhomboids from different organisms.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Serina Proteinasa
/
Proteínas de Escherichia coli
/
Benzoxazinas
/
Proteínas de Unión al ADN
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Bélgica