1.
Bioorg Med Chem Lett
; 19(9): 2386-91, 2009 May 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-19356929
RESUMEN
An effort aimed at exploring structural diversity in the N-pyrazole-N'-naphthylurea class of p38 kinase inhibitors led to the synthesis and characterization of N-phenyl-N'-naphthylureas. Examples of these compounds displayed excellent inhibition of TNF-alpha production in vitro, as well as efficacy in a mouse model of lipopolysaccharide induced endotoxemia. In addition, perspective is provided on the role of a sulfonamide functionality in defining inhibitor potency.
Asunto(s)
2-Naftilamina/análogos & derivados , Inhibidores de Proteínas Quinasas/farmacología , Urea/análogos & derivados , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , 2-Naftilamina/química , Animales , Química Orgánica/métodos , Química Farmacéutica/métodos , Cristalografía por Rayos X/métodos , Diseño de Fármacos , Concentración 50 Inhibidora , Lipopolisacáridos/metabolismo , Ratones , Modelos Químicos , Estructura Molecular , Factor de Necrosis Tumoral alfa/metabolismo , Urea/química
2.
Bioorg Med Chem Lett
; 17(16): 4664-9, 2007 Aug 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-17576063
RESUMEN
The discovery of a series of potent, carboline-based MK2 inhibitors is described. These compounds inhibit MK2 with IC50s as low as 10 nM, as measured in a DELFIA assay. An X-ray crystal structure reveals that they bind in a region near the p-loop and the hinge region of MK2a.