title: Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis.
abstract: High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.
authors.affiliation: Bristol Myers Squibb Company , P.O. Box 4000, Princeton, New Jersey 08543-4000, United States.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Santella
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Gardner
authors.forename: John V
authors.initials: JV
authors.lastname: Duncia
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Murali
authors.initials: M
authors.lastname: Dhar
authors.forename: Cullen
authors.initials: C
authors.lastname: Cavallaro
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tebben
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.forename: Melissa
authors.initials: M
authors.lastname: Yarde
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Briceno
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Cvijic
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: Watson
authors.forename: Guchen
authors.initials: G
authors.lastname: Yang
authors.forename: Anne V
authors.initials: AV
authors.lastname: Rose
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Vickery
authors.forename: Janet
authors.initials: J
authors.lastname: Caceres-Cortes
authors.forename: Christian
authors.initials: C
authors.lastname: Caporuscio
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Camac
authors.forename: Javed A
authors.initials: JA
authors.lastname: Khan
authors.forename: Yongmi
authors.initials: Y
authors.lastname: An
authors.forename: William R
authors.initials: WR
authors.lastname: Foster
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: John
authors.initials: J
authors.lastname: Hynes
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001682:Biological Availability; D017322:Clinical Trials, Phase II as Topic; D055808:Drug Discovery; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D010880:Piperidines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000077297:Pregnane X Receptor; D011487:Protein Conformation; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D013045:Species Specificity; D014508:Urea / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C000593258:1-(1-(4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-(2-hydroxy-2-methylpropyl)urea; D010880:Piperidines; D000077297:Pregnane X Receptor; D054389:Receptors, CCR1; D011987:Receptors, Steroid; D014508:Urea; D014633:Valine