Novel pirfenidone analogues: Synthesis of pyridin-2-ones for the treatment of pulmonary fibrosis

Abstract

A new series of polysubstituted 1-aryl-2-oxo-1,2-dihydropyridine-3- carbonitriles and pyrazolo[3,4-b]pyridine-5-carbonitriles and pyrido[2,3-d]pyrimidine-6-carbonitriles have been synthesized and tested for their antifibrotic activity. Among the tested compounds, compounds IIc and IVb exhibited higher antifibrotic activity than the standard pirfenidone PD with a reduction of the hydroxyproline level to 50 and 140 μmol/lung, respectively. However, bicyclic pyridone VIIIb displayed a high mortality rate. Detailed syntheses, spectroscopic and biological data are reported. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.