title: Discovery and synthesis of cyclohexenyl derivatives as modulators of CC chemokine receptor 2 activity.
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.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States. Electronic address: gregory.brown@bms.com.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Brown
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: George V
authors.initials: GV
authors.lastname: Delucca
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Batt
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Galella
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Cvijic
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Rui-Qin
authors.initials: RQ
authors.lastname: Liu
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543-4000, United States.
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
mesh_terms: D053138:Cyclohexenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D053138:Cyclohexenes; D054390:Receptors, CCR2
keywords: CCR2; CCR2 antagonist; Chemokine; GPCR