Benzimidazoles as benzamide replacements within cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists

Robert J Cherney; Ruowei Mo; Dayton T Meyer; Anthony D Pechulis; Michael A Guaciaro; Yvonne C Lo; Gengjie Yang; Persymphonie B Miller; Peggy A Scherle; Qihong Zhao; Mary Ellen Cvijic; Joel C Barrish; Carl P Decicco; Percy H Carter

doi:10.1016/j.bmcl.2012.08.002

Benzimidazoles as benzamide replacements within cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6181-4. doi: 10.1016/j.bmcl.2012.08.002. Epub 2012 Aug 10.

Authors

Robert J Cherney¹, Ruowei Mo, Dayton T Meyer, Anthony D Pechulis, Michael A Guaciaro, Yvonne C Lo, Gengjie Yang, Persymphonie B Miller, Peggy A Scherle, Qihong Zhao, Mary Ellen Cvijic, Joel C Barrish, Carl P Decicco, Percy H Carter

Affiliation

¹ Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, United States. [email protected]

PMID: 22939233
DOI: 10.1016/j.bmcl.2012.08.002

Abstract

We describe the design, synthesis, and evaluation of benzimidazoles as benzamide replacements within a series of trisubstituted cyclohexane CCR2 antagonists. 7-Trifluoromethylbenzimidazoles displayed potent binding and functional antagonism of CCR2 while being selective over CCR3. These benzimidazoles were also incorporated into lactam-containing antagonists, thus completely eliminating the customary bis-amide.

MeSH terms

Benzimidazoles / chemical synthesis
Benzimidazoles / chemistry
Benzimidazoles / pharmacology*
Cyclohexanes / chemistry*
Dose-Response Relationship, Drug
Drug Design
Humans
Microsomes / drug effects
Molecular Structure
Receptors, CCR2 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Benzimidazoles
CCR2 protein, human
Cyclohexanes
Receptors, CCR2
Cyclohexane