Synthesis, bioassay, and QSAR study of bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles

•Pyrano[3,2-c]pyridines were synthesized in a facile synthetic approach.•Bronchodilation properties of the pyrano[3,2-c]pyridines were reported.•Many of the compounds synthesized exhibit promising activity compared with theophylline.•A significant QSAR model was explored describing the bronchodilation activity.

A statistically significant QSAR model describing the bioactivity of bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles (N = 41, n = 8, R2 = 0.824, R2cv = 0.724, F = 18.749, s2 = 0.0018) was obtained employing CODESSA-Pro software. The bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles 17–57 were synthesized through a facile approach via reaction of 1-alkyl-4-piperidones 1–4 with ylidenemalononitriles 5–16 in methanol in the presence of sodium. The bronchodilation properties of 17–57 were investigated in vitro using isolated guinea pig tracheal rings pre-contracted with histamine (standard method) and compared with theophylline (standard reference). Most of the compounds synthesized exhibit promising bronchodilation properties especially, compounds 25 and 28.

Graphical abstractA statistically significant QSAR model describing the bioactivity of bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles.Figure optionsDownload full-size imageDownload as PowerPoint slide