RESUMEN

Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 A internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.

Asunto(s)

Antineoplásicos/síntesis química , Benzamidas/síntesis química , Inhibidores de Histona Desacetilasas , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , Antineoplásicos/química , Benzamidas/química , Benzamidas/farmacología , Dominio Catalítico , Línea Celular , Histona Desacetilasa 1 , Histona Desacetilasas/química , Histona Desacetilasas/metabolismo , Humanos , Modelos Moleculares , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/metabolismo , Relación Estructura-Actividad