Discovery and structure–activity relationships of urea derivatives as potent and novel CCR3 antagonists

The synthesis and structure–activity relationships of ureas as CCR3 antagonists are described. Optimization starting with lead compound 2 (IC50=190nM) derived from initial screening hit compound 1 (IC50=600nM) led to the identification of (S)-N-((1R,3S,5S)-8-((6-fluoronaphthalen-2-yl)methyl)-8-azabicyclo[3.2.1]octan-3-yl)-N-(2-nitrophenyl)pyrrolidine-1,2-dicarboxamide 27 (IC50=4.9nM) as a potent CCR3 antagonist.