title: Discovery of an orally-bioavailable CC Chemokine Receptor 2 antagonist derived from an acyclic diaminoalcohol backbone.
abstract: We describe an isostere-driven approach to improve upon a previously-described series of capped dipeptide antagonists of CC Chemokine Receptor 2 (CCR2). Modification of the substitution around the isostere was combined with additional changes in a distal aromatic substituent to provide single-digit nanomolar antagonists of CCR2. These studies led to the identification of 18, a compound that was suitable for studies in murine models of CCR2 activity.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, United States. percy.carter@bms.com
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Brown
authors.forename: Sarah R
authors.initials: SR
authors.lastname: King
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Voss
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tebben
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cherney
authors.forename: Sandhya
authors.initials: S
authors.lastname: Mandlekar
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: Qihong
authors.initials: Q
authors.lastname: Zhao
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
mesh_terms: D000605:Amino Alcohols / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D051379:Mice; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*
chemical_list: D000605:Amino Alcohols; D054390:Receptors, CCR2