RESUMEN

The SAR and improvement in potency against Tie2 of novel thienopyrimidine and thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one of these compounds bound to the Tie-2 kinase domain is consistent with the SAR. These compounds have moderate potency in cellular assays of Tie-2 inhibition, good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.

Asunto(s)

Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Receptor TIE-2/antagonistas & inhibidores , Tiazoles/farmacología , Cristalografía por Rayos X , Diseño de Fármacos , Humanos , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Pirimidinas/síntesis química , Pirimidinas/química , Estereoisomerismo , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/química