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

Abstract

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.

DOI: 10.1016/j.bmcl.2011.01.052

Cite this paper

@article{Trujillo2011DesignAS, title={Design and synthesis of novel CCR2 antagonists: investigation of non-aryl/heteroaryl binding motifs.}, author={J. Trujillo and Wei Huang and Robert O Hughes and D Joseph Rogier and S Richard Turner and Rajesh V Devraj and Philip A Morton and C B Xue and Ganfeng Chao and Maryanne B. Covington and Robert C. Newton and Brian W. Metcalf}, journal={Bioorganic & medicinal chemistry letters}, year={2011}, volume={21 6}, pages={1827-31} }