RESUMEN
The link between PDE4 and apoptosis prompted us to design and synthesize for the first time a series of novel 1-thienyl pyrroloquinoxalines as potential PDE4 inhibitors/apoptotic agents. A ligand-free Pd-catalyzed C-N cross-coupling/cyclization strategy has been developed for the rapid and milder access to this class of compounds some of which showed interesting pharmacological properties when tested in vitro and in zebrafish embryos.
Asunto(s)
Apoptosis/efectos de los fármacos , Paladio/química , Inhibidores de Fosfodiesterasa 4/farmacología , Pirroles/farmacología , Quinoxalinas/farmacología , Tiofenos/farmacología , Animales , Catálisis , Ciclización , Relación Dosis-Respuesta a Droga , Estructura Molecular , Inhibidores de Fosfodiesterasa 4/síntesis química , Inhibidores de Fosfodiesterasa 4/química , Pirroles/síntesis química , Pirroles/química , Quinoxalinas/síntesis química , Quinoxalinas/química , Relación Estructura-Actividad , Tiofenos/síntesis química , Tiofenos/química , Pez Cebra/embriologíaRESUMEN
A facile construction of a thiophene ring fused with N-heterocycles has been achieved via the reaction of NaSH with 2-chloro-3-alkynyl quinoxalines/pyrazines leading to novel 2-substituted thieno[2,3-b]pyrazine/quinoxaline derivatives as potential inducers of apoptosis. Some of them showed encouraging pharmacological properties when tested in zebrafish.
Asunto(s)
Apoptosis/efectos de los fármacos , Compuestos Heterocíclicos/química , Bibliotecas de Moléculas Pequeñas/farmacología , Sulfuros/química , Tiofenos/farmacología , Animales , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Modelos Moleculares , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad , Tiofenos/síntesis química , Tiofenos/química , Pez Cebra/embriologíaRESUMEN
For the first time TFAA/H3PO4 has facilitated the direct and metal-free N-acylation of carbazoles leading to a number of N-acylated derivatives. Several of these compounds were found to be promising when tested for their anti-proliferative properties against oral cancer cell lines.