The cFMS inhibitory activity of 2´-aminoanilide derivatives has been quantitatively analyzed in terms of Dragon descriptors using CP-MLR. The analysis has provided a rational approach for the development of new 2´-aminoanilide   derivatives, the cFMS inhibitors, as potential anti-inflammatory agents. The descriptors identified in CP-MLR analysis have highlighted the role of atomic properties in respective lags of 2D-autocorrelations (MATS7m, MATS5v and GATS2p), path/walk ratio 2-Randic shape index (PW2) and Lovasz-Pelikans’ leading eigenvalue index (LP1) to explain the biological actions of 2´-aminoanilide derivatives as cFMS inhibitors. Certain structural fragment (C-001) and functionality (nCrHR) in molecular structures have also shown prevalence to optimize the cFMS inhibitory activity of titled compounds. Applicability domain analysis revealed that the suggested model matches the high quality parameters with good fitting power and the capability of assessing external data and all of the compounds was within the applicability domain of the proposed model and were evaluated correctly.