Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series

SAR studies were conducted around lead compound 1 using high-throughput parallel solution and solid phase synthesis. Our lead optimization efforts led to the identification of several CCR2b antagonists with potent activity in both binding and functional assays [Compound 71 CCR2b Binding IC50 3.2 nM; MCP-1-Induced Chemotaxis IC50 0.83 nM; Ca2+ Flux IC50 7.5 nM].

Graphical abstractSAR studies of a 3-amino pyrrolidine series led to the identification of potent CCR2b antagonists with low nanomolar activity in binding and functional assays as exemplified by compound 71.Figure optionsDownload full-size imageDownload as PowerPoint slide