Design, synthesis, and structure-activity-relationship of a novel series of CXCR4 antagonists

A novel series of CXCR4 antagonists was developed by a scaffold hybridization strategy. The most promising lead of this series, compound 3, binds potently with CXCR4 receptor (IC50 = 54 nM) and inhibits CXCL12 induced cytosolic calcium increase (IC50 = 2.3 nM). Furthermore, compound 3 possesses good physicochemical properties (MW 353, clogP 2.0, PSA 48, pKa 6.7), exhibits minimal CYP isozyme and hERG inhibition.93