Quantitative structure activity relationship and pharmacophore studies of adenosine receptor A2B inhibitors.

Adenosine receptor A2B (ADoR A2B) is an important G protein-coupled receptor (GPCR) of the rhodopsin family, and plays a pivotal role in gastrointestinal, neurological and hypersensitive disorders. QSAR and pharmacophore studies were carried out using 63 ADoR A2B inhibitor molecules to characterize molecular features and structural requirements for biological interaction. QSAR modelling using genetic algorithm- partial least squares (G/PLS) method identified molecular shape, size electrophilicity and conformational flexibility as important descriptors for these compounds affinity to the receptor. Further analysis of pharmacophore model revealed hydrogen bond acceptor (HBA), hydrogen bond donor (HBD), hydrophobic aliphatic (HY-ala) and hydrophobic aromatic (HY-aro) as the crucial molecular features that predict binding affinity of these compounds to ADoR A2B. These observations provide important insights to the rationale development of novel and potent compounds against ADoR A2B.