QSAR and pharmacophore modeling of 4-arylthieno [3, 2-d] pyrimidine derivatives against adenosine receptor of Parkinson's disease

A series of 47, 4-arylthieno[3, 2-d] pyrimidine derivatives was subjected to quantitative structure-antiparkinson activity relationships (QSAR) studies to evaluate the antagonist activity towards both adenosine A1 and adenosine A2A targets in Parkinson's drug discovery. QSAR models were derived with the aid of genetic function approximation (GFA) technique using descriptors to make connections between structural parameters and antiparkinson's activity followed by ADMET analysis and pharmacophore model generation. QSAR model was assessed using a test set of 12 compounds for A1 (r2 pred = 0.961), (q2 = 0.912) and 12 compounds for A2a (r2 pred = 0.914), (q2 = 0.781) receptor. The results revealed the significant role of DIPOLE MAG, CHI-V-3-P, WIENER, AREA, SC-2 and PHI-MAG descriptors in the antiparkinson activity of the studied compounds against adenosine A1 and adenosine A2A receptors. Subsequent, ADMET analysis shows 28 compounds can be the better candidates of drug and execution of pharmacophore model, explores the hydrogen bond donor, aromatic ring and hydrophobic groups are the key structural features for the antagonist activity. © 2010 World Scientific Publishing Company.