Discovery and SAR of 5-aminooctahydrocyclopentapyrrole-3a-carboxamides as potent CCR2 antagonists

Chaozhong Cai; Dave F McComsey; Cuifen Hou; John C O'Neill; Evan Opas; Sandra McKenney; Dana Johnson; Zhihua Sui

doi:10.1016/j.bmcl.2013.05.024

Discovery and SAR of 5-aminooctahydrocyclopentapyrrole-3a-carboxamides as potent CCR2 antagonists

Bioorg Med Chem Lett. 2014 Feb 15;24(4):1239-42. doi: 10.1016/j.bmcl.2013.05.024. Epub 2013 Jun 28.

Authors

Chaozhong Cai¹, Dave F McComsey², Cuifen Hou², John C O'Neill², Evan Opas², Sandra McKenney², Dana Johnson², Zhihua Sui²

Affiliations

¹ Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA. Electronic address: ccai@its.jnj.com.
² Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.

PMID: 23916257
DOI: 10.1016/j.bmcl.2013.05.024

Abstract

SAR study of 5-aminooctahydrocyclopentapyrrole-3a-carboxamide scaffold led to identification of several CCR2 antagonists with potent activity in both binding and functional assays. Their cardiovascular safety and pharmacokinetic properties were also evaluated.

Keywords: 1,3-Dipolar cycloaddition; CCR2 antagonist; Carbamate; Optimization.

MeSH terms

Cyclopentanes / chemical synthesis
Cyclopentanes / chemistry
Cyclopentanes / pharmacology*
Dose-Response Relationship, Drug
Drug Discovery*
Humans
Molecular Conformation
Pyrroles / chemical synthesis
Pyrroles / chemistry
Pyrroles / pharmacology*
Receptors, CCR2 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

5-aminooctahydrocyclopentapyrrole-3a-carboxamide
CCR2 protein, human
Cyclopentanes
Pyrroles
Receptors, CCR2