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.

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