RESUMEN
2-Azetidinones, commonly known as beta-lactams, are well-known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel beta-lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform-selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone-ring nitrogen atom substituent. The presence of an N-thiomethyl group is a prerequisite for the activity of these compounds in the micromolar range towards HDAC8.
Asunto(s)
Azetidinas/química , Azetidinas/farmacología , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Zinc/metabolismo , Azetidinas/síntesis química , Inhibidores de Histona Desacetilasas/síntesis química , Histona Desacetilasas/química , Humanos , Modelos Moleculares , Estructura Molecular , Unión Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Relación Estructura-ActividadRESUMEN
Remarkable generality in scope of DATs/Cu catalysts for enantioselective nitroaldol reaction is described; excellent levels of stereoinduction are recorded for a range of aldehydes (ee 81-99%, 17 examples) and the possibility to employ the present catalytic system as the key step for the preparation of highly functionalized tetrahydro-isoquinolines is demonstrated.
