Palladium-catalyzed cross-coupling reactions on a bromo-naphthalene scaffold in the search for novel human CC chemokine receptor 8 (CCR8) antagonists

Abstract

The naphthalene sulfonamide scaffold is known to possess CCR8 antagonistic properties. In order to expand the structure–activity relationship study of this compound class, a variety of palladium-catalyzed cross-coupling reactions was performed on a bromo-naphthalene precursor yielding a diverse library. These compounds displayed CCR8 antagonistic properties in binding and calcium mobilization assays, with IC50 values in the 0.2 – 10 µM range. The decreased activity, when compared to the original lead compound, was rationalized by homology molecular modeling.