dihydropyridines and Pulmonary-Fibrosis

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 micromol/lung, respectively. However, bicyclic pyridone VIIIb displayed a high mortality rate. Detailed syntheses, spectroscopic and biological data are reported.

Topics: Administration, Oral; Alanine Transaminase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspartate Aminotransferases; Bleomycin; Bronchoalveolar Lavage Fluid; Creatinine; Dihydropyridines; Disease Models, Animal; Hydroxyproline; Intubation, Intratracheal; L-Lactate Dehydrogenase; Lung; Male; Molecular Structure; Pulmonary Fibrosis; Pyridones; Rats; Time Factors; Urea