The p38α mitogen-activated protein kinase (MAPK) has become an attractive target for the treatment of many diseases such as rheumatoid arthritis, inflammatory bowel disease and Crohn’s disease. In this paper, 3D-QSAR and molecular docking studies were performed on 59 p38α MAPK inhibitors. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to determine the structural requirements for potency in inhibiting p38α MAPK. The resulting model of CoMFA and CoMSIA exhibited good r2cv values of 0.725 and 0.609, and r2 values of 0.961 and 0.905, respectively. Molecular docking was used to explore the binding mode between the inhibitors and p38α MAPK. We have accordingly designed a series of novel p38α MAPK inhibitors by utilizing the structure-activity relationship (SAR) results revealed in the present study, which were predicted with excellent potencies in the developed models. The results provided a useful guide to design new compounds for p38α MAPK inhibitors.

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The pyrrolopyrimidine derivatives have been regarded as a novel class of LIM-kinase 2 inhibitor. To explore the relationship between the structures of substituted pyrrolopyrimidine derivatives and their inhibitory activities against LIMK2, CoMFA and CoMSIA analyses, and molecular docking studies were performed on a dataset of forty-one compounds. The two 3D-QSAR models resulted from thirty-one molecules in the training set gave r 2 cv values of 0.635 and 0.660, r 2 values of 0.973 and 0.965, respectively. The predictive ability of CoMFA and CoMSIA, determined using a test set of ten compounds, gave predictive correlation coefficients of 0.971 and 0.964, respectively. 3D contour maps generated from CoMFA and CoMSIA along with the docking binding structures provided enough information about the structural requirements for better activity. The results can serve as a useful guideline to design novel LIMK2 inhibitors with better potencies.