Design and synthesis of novel CCR2 antagonists: Investigation of non-aryl/heteroaryl binding motifs

This report describes the design and synthesis of a series of CCR2 antagonists incorporating novel non-aryl/heteroaryl RHS (right hand side) motifs. Previous SAR in the area has suggested an aryl/heteroaryl substituent as a necessary structural feature for binding to the CCR2 receptor. Herein we describe the SAR with regards to potency (binding to hCCR2), dofetilide activity and metabolic stability (in vitro HLM) for this series. The resulting outcome was the identification of compounds with excellent properties for the investigation of the role of CCR2 in disease.

Graphical abstractThis report describes the design and synthesis of a series of CCR2 antagonists incorporating non-aryl/heteroaryl RHS motifs and a 2.2.1 ring system.Figure optionsDownload full-size imageDownload as PowerPoint slide