title: Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists.
abstract: Potent sulfone-containing di- and trisubstituted cyclohexanes were synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. This led to the trisubstituted derivative 54, which exhibited excellent binding (CCR2 IC(50)=1.3nM) and functional antagonism (calcium flux IC(50)=0.5nM and chemotaxis IC(50)=0.2nM). The superiority of the trisubstituted scaffold was rationalized to be the result of a conformational rigidification, which provided insight into the bioactive conformation of this chemotype.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, United States. robert.cherney@bms.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cherney
authors.forename: Ruowei
authors.initials: R
authors.lastname: Mo
authors.forename: Dayton T
authors.initials: DT
authors.lastname: Meyer
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Voss
authors.forename: Yvonne C
authors.initials: YC
authors.lastname: Lo
authors.forename: Gengjie
authors.initials: G
authors.lastname: Yang
authors.forename: Persymphonie B
authors.initials: PB
authors.lastname: Miller
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Scherle
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tebben
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
mesh_terms: D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D054390:Receptors, CCR2; D013450:Sulfones