In silico accounting of novel pyridazine analogues as h-PTP 1B inhibitors: pharmacophore modelling, atom-based 3D QSAR and docking studies

Abstract

PTP 1B, a negative regulator of insulin signalling pathway, has been rigorously investigated for its potential for design and development of drugs for the management of type 2 diabetes. Pharmacophore modelling, atom-based 3D QSAR and docking studies were performed on a series of 37 pyridazine derivatives reported as PTP 1B inhibitors. A five-point pharmacophore model consisting of two hydrogen bond acceptors (A), one hydrogen bond donor (D), one hydrophobic (H) and one aromatic ring (R) with discrete geometries as pharmacophoric features were developed for a predictive 3D QSAR model. The robustness of the generated model was validated by good correlation coefficient value (r2 = 0.832), Pearson-R value (0.8593), cross-validated correlation coefficient (q2 = 0.663). This study investigated some of the indispensible structural features of pyridazine analogues which can further be exploited to optimize h-PTP 1B inhibitors.