QSAR Studies on Pyridazinopyridinone Derivatives against P38 Mitogen-Activated Protein Kinase

Radha Mahendran, Nagasoundarya Rajendran, Suganya Jeyabasker and Vardhini Viswanathan

P38Mitogen-Activated Protein Kinase (MAPK) belongs to serine/threonine protein kinases family, which shows inflammatory effects in the preclinical disease models. A Number of structurally diverse p38 MAP Kinase develops into Rheumatoid Arthritis agents. Most of the inhibitors have failed due to poor pharmacokinetic profile or selectivity issue, which makes p38 MAPK a promising target for QSAR studies. Recent research has proved Pyridazinopyridinone compounds to be novel p38 Mitogen-Activated Protein Kinase Inhibitors. In the present study, Quantitative Structure-Activity-Relationship (QSAR) study on pyridazinopyridinone derivatives has been carried out using BUILDQSAR software. Linear regression QSAR models of the biological activity (Ki) of 23 pyridazinopyridinone derivatives of p38 MAPK were established with 6 different molecular descriptors. The descriptors were selected by following Lipinski’s rule of five. Among the models presented in this study, Lig29, Lig32, and Lig37 appeared to be in regression line of Multiple Linear Regression (MLR) analysis. Whereas Lig37appeared to be inmore than one descriptor graph, therefore, Lig37 of the pyridazinopyridinone derivatives could emerge as a potent inhibitor of the p38 Mitogen Activator Protein Kinase (MAPK) which could play a vital role in the treatment of Rheumatoid Arthritis.

Volume 11 | 04-Special Issue

Pages: 700-707