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

Adel S Girgis; Dalia O Saleh; Riham F George; Aladdin M Srour; Girinath G Pillai; Chandramukhi S Panda; Alan R Katritzky

doi:10.1016/j.ejmech.2013.12.032

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

Eur J Med Chem. 2015 Jan 7:89:835-43. doi: 10.1016/j.ejmech.2013.12.032. Epub 2014 Jan 3.

Authors

Adel S Girgis¹, Dalia O Saleh², Riham F George³, Aladdin M Srour⁴, Girinath G Pillai⁵, Chandramukhi S Panda⁶, Alan R Katritzky⁷

Affiliations

¹ Pesticide Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
² Pharmacology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
³ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁴ Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
⁵ Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA; Department of Chemistry, University of Tartu, Ravila 14a, Tartu 50411, Estonia.
⁶ Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
⁷ Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA; Department of Chemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: katritzky@chem.ufl.edu.

PMID: 25462283
DOI: 10.1016/j.ejmech.2013.12.032

Abstract

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.

Keywords: 4-Piperidone; 4H-Pyrano[3,2-c]pyridine-3-carbonitrile; Bronchodilation; QSAR; Ylidenemalononitrile.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biological Assay
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*
Quantitative Structure-Activity Relationship*
Software

Substances

Bronchodilator Agents
Pyrans
Pyridines