RESUMEN
Erythropoietin-producing hepatocellular receptor tyrosine kinase subtype A2 (EphA2) is an attractive therapeutic target for suppressing tumor progression. In our efforts to discover novel small molecules to inhibit EphA2, a class of compound based on 4-substituted quinazoline containing 7-(morpholin-2-ylmethoxy) group was identified as a novel hit by high throughput screening campaign. Structural modification of parent quinazoline scaffolds by introducing substituents on aniline displayed potent inhibitory activities toward EphA2.
Asunto(s)
Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Receptor EphA2/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Quinazolinas/síntesis química , Quinazolinas/química , Receptor EphA2/metabolismo , Relación Estructura-ActividadRESUMEN
A series of hydroxybenzoxazole derivatives was synthesized, and their c-Met kinase inhibitory activity was evaluated. Described herein is a potent c-Met inhibitor by structural modification of the parent benzoxazole scaffold, with particular focus on the hydroxyl substituent of the benzoxazole moiety.
Asunto(s)
Aminopiridinas/síntesis química , Antineoplásicos/síntesis química , Benzoxazoles/síntesis química , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Aminopiridinas/farmacología , Antineoplásicos/farmacología , Benzoxazoles/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Simulación por Computador , Humanos , Modelos Moleculares , Proteínas Proto-Oncogénicas c-met/química , Relación Estructura-Actividad , Tirosina Quinasa 3 Similar a fms/químicaRESUMEN
A series of 3-(4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-2-yl)-1H-quinolin-2-ones have been identified as a new class of VEGFR-2 kinase inhibitors. A variety of (4,5,6,7-tetrahydro-imidazo[5,4-c]pyridin-2-yl)-acetic acid ethyl esters were synthesized, and their VEGFR-2 inhibitory activity was evaluated. Described herein are the preparation of the series and the effects of the compounds on VEGFR-2 kinase activity.