RESUMO
We describe in this Letter a new synthetic method for pyrrolin-2-ones as potent plasminogen activator inhibitor-1 (PAI-1) inhibitors. Pyrrolin-2-one derivatives synthesized from N-2-oxoethylamides and aldehydes in aqueous NaOH by one-pot were evaluated for their PAI-1 inhibitory activity. Among these derivatives, compounds 16 and 18 were found to possess potent PAI-1 inhibitory activity (compound 16: IC(50): 0.69microM, compound 18: IC(50): 0.65microM).
Assuntos
Acrilatos/síntese química , Fibrinolíticos/síntese química , Inibidor 1 de Ativador de Plasminogênio/química , Pirrolidinonas/síntese química , Inibidores de Serina Proteinase/química , Acrilatos/química , Acrilatos/farmacologia , Desenho de Fármacos , Fibrinolíticos/química , Fibrinolíticos/farmacologia , Humanos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Pirrolidinonas/química , Pirrolidinonas/farmacologia , Inibidores de Serina Proteinase/metabolismoRESUMO
A novel series of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives has been prepared. These compounds showed potent PDE4 inhibitory activities and a broad margin between the K(i) value of the rolipram binding affinity and the IC(50) value of PDE4 inhibition. They also exhibited potent inhibitory activities toward LPS-induced TNF-alpha production in mice.
