Design, synthesis and SAR of indazole and benzoisoxazole containing 4-azetidinyl-1-aryl-cyclohexanes as CCR2 antagonists

Xuqing Zhang; Heather Hufnagel; Cuifen Hou; Evan Opas; Sandra McKenney; Carl Crysler; John O'Neill; Dana Johnson; Zhihua Sui

doi:10.1016/j.bmcl.2011.08.074

Design, synthesis and SAR of indazole and benzoisoxazole containing 4-azetidinyl-1-aryl-cyclohexanes as CCR2 antagonists

Bioorg Med Chem Lett. 2011 Oct 15;21(20):6042-8. doi: 10.1016/j.bmcl.2011.08.074. Epub 2011 Aug 22.

Authors

Xuqing Zhang¹, Heather Hufnagel, Cuifen Hou, Evan Opas, Sandra McKenney, Carl Crysler, John O'Neill, Dana Johnson, Zhihua Sui

Affiliation

¹ Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19477, United States. xzhang5@prdus.jnj.com

PMID: 21917454
DOI: 10.1016/j.bmcl.2011.08.074

Abstract

A novel series of 4-azetidinyl-1-aryl-cyclohexanes containing indazole or benzoisoxazole moiety have been identified as potent CCR2 antagonists with high selectivity versus hERG.

MeSH terms

Animals
Cell Line
Cyclohexanes / chemical synthesis
Cyclohexanes / chemistry
Cyclohexanes / pharmacokinetics
Cyclohexanes / pharmacology
Dogs
Drug Design
Humans
Indazoles / chemical synthesis
Indazoles / chemistry*
Indazoles / pharmacokinetics
Indazoles / pharmacology*
Oxazoles / chemical synthesis
Oxazoles / chemistry*
Oxazoles / pharmacokinetics
Oxazoles / pharmacology*
Rats
Receptors, CCR2 / antagonists & inhibitors*
Receptors, CCR2 / metabolism
Structure-Activity Relationship
Trans-Activators / metabolism
Transcriptional Regulator ERG

Substances

Cyclohexanes
ERG protein, human
Indazoles
Oxazoles
Receptors, CCR2
Trans-Activators
Transcriptional Regulator ERG