Discovery of N-propylurea 3-benzylpiperidines as selective CC chemokine receptor-3 (CCR3) antagonists

Abstract The discovery of novel and selective small molecule antagonists of the CC Chemokine Receptor-3 (CCR3) is presented. Simple conversion from a 4- to 3-benzylpiperidine gave improved selectivity for CCR3 over the serotonin 5HT 2A receptor. Chiral resolution and exploration of mono- and disubstitution of the N -propylurea resulted in several 3-benzylpiperidine N -propylureas with CCR3 binding IC 50 s under 5 nM. Data from in vitro calcium mobilization and chemotaxis assays for these compounds ranged from high picomolar to low nanomolar EC 50 s and correlated well with antagonist binding IC 50 s.