Quantitative structure–activity relationships for small non-peptide antagonists of CXCR2: Indirect 3D approach using the frontal polygon method Original Research Article

The chemokine receptor, CXCR2, plays an important role in recruiting granulocytes to sites of inflammation and has been proposed as an important therapeutic target. A number of CXCR2 antagonists have been synthesized and evaluated; however, quantitative structure–activity relationship (QSAR) models have not been developed for these molecules. Most CXCR2 antagonists can be grouped into four related categories: N,N′-diphenylureas, nicotinamide N-oxides, quinoxalines, and triazolethiols. Based on these categories, we developed a QSAR model for 59 nonpeptide antagonists of CXCR2 using a partial 3D comparison of the antagonists with local fingerprints obtained from rigid and flexible fragments of the molecules. Each compound was represented by calculated structural descriptors that encoded atomic charge, molar refraction, hydrophobicity