RESUMO
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.
Assuntos
Apoptose/efeitos dos fármacos , Paládio/química , Inibidores da Fosfodiesterase 4/farmacologia , Pirróis/farmacologia , Quinoxalinas/farmacologia , Tiofenos/farmacologia , Animais , Catálise , Ciclização , Relação Dose-Resposta a Droga , Estrutura Molecular , Inibidores da Fosfodiesterase 4/síntese química , Inibidores da Fosfodiesterase 4/química , Pirróis/síntese química , Pirróis/química , Quinoxalinas/síntese química , Quinoxalinas/química , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/química , Peixe-Zebra/embriologiaRESUMO
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.
