title: The discovery of BMS-457, a potent and selective CCR1 antagonist.
abstract: A series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis.
authors.affiliation: Bristol-Myers Squibb Company, R&D, P.O. Box 4000, Princeton, NJ 08543-4000, USA. daniel.gardner@bms.com
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Gardner
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Santella
authors.forename: John V
authors.initials: JV
authors.lastname: Duncia
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
authors.forename: T G Murali
authors.initials: TG
authors.lastname: Dhar
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Guo
authors.forename: Cullen
authors.initials: C
authors.lastname: Cavallaro
authors.forename: Katy
authors.initials: K
authors.lastname: Van Kirk
authors.forename: Melissa
authors.initials: M
authors.lastname: Yarde
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Briceno
authors.forename: R Robert
authors.initials: RR
authors.lastname: Grafstrom
authors.forename: Richard
authors.initials: R
authors.lastname: Liu
authors.forename: Sima R
authors.initials: SR
authors.lastname: Patel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tebben
authors.forename: Dan
authors.initials: D
authors.lastname: Camac
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.forename: Andrew
authors.initials: A
authors.lastname: Watson
authors.forename: Guchen
authors.initials: G
authors.lastname: Yang
authors.forename: Anne
authors.initials: A
authors.lastname: Rose
authors.forename: William R
authors.initials: WR
authors.lastname: Foster
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Cvijic
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: John
authors.initials: J
authors.lastname: Hynes
mesh_terms: D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C585540:BMS-457; D010880:Piperidines; D054389:Receptors, CCR1