Investigation of structure–activity relationship: In silico studies of [1, 2, 4]triazolo[4, 3-a]pyridine ureas as P38 kinase inhibitors

P38 kinases are the members of serine/threonine family and play a vital role in progression inflammation. In past two decades, numerous p38 kinase inhibitors have been reported, few them failed clinical trials. Recently, some entered trials for treatment Alzheimer’s disease. A potential opportunity exists medicinal chemistry discovery potent safe inhibitors. view this challenging opportunity, present manuscript is aimed towards development 3D quantitative structure–activity relationship (QSAR) model docking dynamic simulation studies. statistically robust QSAR was developed by employing 21 training set molecules which attributed with appreciating cross-validation coefficient (q2) 0.0.6269 conventional correlation (r2) 0.8783 respectively. The predicted (r2 pred) found to be 0.8644 standard error 0.3331. molecular analysis all revealed that analogs were well docked into DFG (Asp-Phe-Gly motif) out pocket exhibited hydrogen bond interactions Asp186 Lys71. Extension studies dynamics study informed ligand displayed strong conformational stability within active site forming maximum bonds until 100 ns