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

• Published in: European journal of medicinal chemistry 2015-01, Vol.89, p.835-843
• Main Authors: Girgis, Adel S., Saleh, Dalia O., George, Riham F., Srour, Aladdin M., Pillai, Girinath G., Panda, Chandramukhi S., Katritzky, Alan R.
• Format: Article
• Language: English
• Subjects: 4-Piperidone; 4H-Pyrano[3,2-c]pyridine-3-carbonitrile; Animals; Biological Assay; Bronchodilation; Bronchodilator Agents - chemical synthesis; Bronchodilator Agents - chemistry; Bronchodilator Agents - pharmacology; Guinea Pigs; Linear Models; Molecular Structure; Pyrans - chemical synthesis; Pyrans - chemistry; Pyrans - pharmacology; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; QSAR; Quantitative Structure-Activity Relationship; Software; Ylidenemalononitrile
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.12.032

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. [Display omitted] A statistically significant QSAR model describing the bioactivity 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.