Discovery and synthesis of cyclohexenyl derivatives as modulators of CC chemokine receptor 2 activity

Gregory D Brown; Qing Shi; George V Delucca; Douglas G Batt; Michael A Galella; Mary-Ellen Cvijic; Rui-Qin Liu; Feng Qiu; Qihong Zhao; Joel C Barrish; Percy H Carter

doi:10.1016/j.bmcl.2015.11.051

Discovery and synthesis of cyclohexenyl derivatives as modulators of CC chemokine receptor 2 activity

Bioorg Med Chem Lett. 2016 Jan 15;26(2):662-666. doi: 10.1016/j.bmcl.2015.11.051. Epub 2015 Nov 17.

Authors

Affiliations

¹ Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States. Electronic address: [email protected].
² Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.

PMID: 26631321
DOI: 10.1016/j.bmcl.2015.11.051

Abstract

A novel cyclohexenyl series of CCR2 antagonists has been discovered. This series of small, rigid compounds exhibits submicromolar binding affinity for CCR2. Modification of the substituents on the cyclohexene ring led to the identification of potent CCR2 antagonists. Progress from initial lead 5 (IC50=700nM) to (-)-38 (IC50=9.0nM) is discussed.

Keywords: CCR2; CCR2 antagonist; Chemokine; GPCR.

MeSH terms

Cyclohexenes / chemical synthesis
Cyclohexenes / chemistry*
Cyclohexenes / pharmacology*
Drug Discovery
Humans
Models, Molecular
Receptors, CCR2 / antagonists & inhibitors*
Receptors, CCR2 / metabolism
Structure-Activity Relationship

Substances

Cyclohexenes
Receptors, CCR2