Abstract
Aim: Synthesis of novel bronchodilatory active indole–pyridine conjugates. Results/methodology: Indole–pyridine conjugates (6a–n, 8a–i and 10a–c) were synthesized in a facile pathway through reaction of 2-[(1-alkyl-1H-indol-3-yl)methylene]malononitriles 4a,b with the corresponding ketone-containing compounds (5a–f, 7a–c and 9a,b) in the presence of sodium alkoxide. Single (6l, 8g) and powder (6k, 8d) x-ray studies supported the structures. Results: Histamine precontracted isolated tracheal rings of guinea pig exhibited the potent bronchodilation properties of 6c (about double-fold potency relative to the standard reference, theophylline). Some of the synthesized conjugates (8d, 6c, 6f and 6e) revealed promising reduction of IL-8 production during lipopolysaccharide-induced airway inflammatory bioassay. Computational studies (3D pharmacophore, 2D-QSAR ‘quantitative structure–activity relationship’) showed high approximations to the bronchodilation properties and explained the parameters controlling biological observations.
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Financial & competing interests disclosure
This work was supported financially by National Research Centre, Egypt, project ID: 11010341. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.