title: Urea based CCR3 antagonists employing a tetrahydro-1,3-oxazin-2-one spacer.
abstract: Conformational restriction of open chain analogs with a more polar tetrahydro-1,3-oxazin-2-one spacer led to the identification of potent urea-based CCR3 antagonists that exhibited excellent selectivity over binding to CYP2D6. The in vitro binding and eosinophil shape change data are presented. Compound 19b exhibited similar selectivity and potency to our development candidate BMS-639623.
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, Princeton, NJ 08543-4000, USA. murali.dhar@bms.com
authors.forename: T G Murali
authors.initials: TG
authors.lastname: Dhar
authors.forename: Guchen
authors.initials: G
authors.lastname: Yang
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: Mary F
authors.initials: MF
authors.lastname: Malley
authors.forename: Jack Z
authors.initials: JZ
authors.lastname: Gougoutas
authors.forename: Dauh-Rurng
authors.initials: DR
authors.lastname: Wu
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
mesh_terms: D048430:Cell Shape / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines; D011485:Protein Binding; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C528978:BMS-639623; D010880:Piperidines; D054397:Receptors, CCR3; D014508:Urea; D019389:Cytochrome P-450 CYP2D6