RESUMEN

The known KDR inhibitor SU5416 and several analogues of the indolin-2-one family were surprisingly found to be highly efficacious in the EAE model, an established model for multiple sclerosis. The high in vivo effect could be correlated to in vitro inhibition of the pro-inflammatory cytokine IL-2. Activity following po administration was obtained with several analogues and via the use of prodrugs.

Asunto(s)

Encefalomielitis Autoinmune Experimental/metabolismo , Indoles/síntesis química , Esclerosis Múltiple/metabolismo , Animales , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Técnicas In Vitro , Indoles/química , Indoles/farmacología , Interleucina-2/antagonistas & inhibidores , Interleucina-2/biosíntesis , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Ratones , Esclerosis Múltiple/tratamiento farmacológico , Relación Estructura-Actividad , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores