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

• DOI: 10.1016/j.ejmech.2013.12.032
• Publication Date: 2014-01-04T01:47:26Z
• Authors: Adel S. Girgis; Dalia O. Saleh; Riham F. George; Aladdin M. Srour; Girinath G. Pillai; Chandramukhi S. P...; Alan R. Katritzky
• Keywords: 0301 basic medicine; Molecular Structure; Pyridines; Guinea Pigs; Quantitative Structure-Activity Relationship; Bronchodilator Agents; 3. Good health; 03 medical and health sciences; Linear Models; Animals; Biological Assay; Software; Pyrans

A statistically significant QSAR model describing the bioactivity of bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles (N = 41, n = 8, R(2) = 0.824, R(2)cv = 0.724, F = 18.749, s(2) = 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.