Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists

Abstract Potent sulfone-containing di- and trisubstituted cyclohexanes were synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. This led to the trisubstituted derivative 54 , which exhibited excellent binding (CCR2 IC 50  = 1.3 nM) and functional antagonism (calcium flux IC 50  = 0.5 nM and chemotaxis IC 50  = 0.2 nM). The superiority of the trisubstituted scaffold was rationalized to be the result of a conformational rigidification, which provided insight into the bioactive conformation of this chemotype.