Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors.
Bioorg Med Chem Lett
; 19(1): 27-30, 2009 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-19058966
ABSTRACT
Endothelial lipase (EL) activity has been implicated in HDL catabolism, vascular inflammation, and atherogenesis, and inhibitors are therefore expected to be useful for the treatment of cardiovascular disease. Sulfonylfuran urea 1 was identified in a high-throughput screening campaign as a potent and non-selective EL inhibitor. A lead optimization effort was undertaken to improve potency and selectivity, and modifications leading to improved LPL selectivity were identified. Radiolabeling studies were undertaken to establish the mechanism of action for these inhibitors, which were ultimately demonstrated to be irreversible inhibitors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Sulfonilurea
/
Furanos
/
Lipasa
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos