title: CC chemokine receptor-3 (CCR3) antagonists: improving the selectivity of DPC168 by reducing central ring lipophilicity.
abstract: DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2D6 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Pruitt
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Batt
authors.forename: Dean A
authors.initials: DA
authors.lastname: Wacker
authors.forename: Lori L
authors.initials: LL
authors.lastname: Bostrom
authors.forename: Shon K
authors.initials: SK
authors.lastname: Booker
authors.forename: Erin
authors.initials: E
authors.lastname: McLaughlin
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Houghton
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Varnes
authors.forename: David D
authors.initials: DD
authors.lastname: Christ
authors.forename: Maryanne
authors.initials: M
authors.lastname: Covington
authors.forename: Anuk M
authors.initials: AM
authors.lastname: Das
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: Danielle
authors.initials: D
authors.lastname: Graden
authors.forename: Ilona
authors.initials: I
authors.lastname: Kariv
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Orlovsky
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Stowell
authors.forename: Krishna G
authors.initials: KG
authors.lastname: Vaddi
authors.forename: Eric A
authors.initials: EA
authors.lastname: Wadman
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Welch
authors.forename: Swamy
authors.initials: S
authors.lastname: Yeleswaram
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Solomon
authors.forename: Robert C
authors.initials: RC
authors.lastname: Newton
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
authors.forename: Soo S
authors.initials: SS
authors.lastname: Ko
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001681:Biological Assay; D002478:Cells, Cultured; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D006801:Humans; D051379:Mice; D002679:Pan troglodytes; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C500084:1-(2-((3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexyl)-3-(3-acetylphenyl)urea; C521493:BMS-570520; D001593:Benzyl Compounds; C515350:CCR3 protein, human; C515351:Ccr3 protein, mouse; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D010671:Phenylurea Compounds; D010880:Piperidines; D054397:Receptors, CCR3; D019707:Receptors, Chemokine