title: CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery and structure-activity relationships.
abstract: CCR3 antagonist leads with IC(50) values in the microM range were converted into low nM binding compounds that displayed in vitro inhibition of human eosinophil chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n-propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n-propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited single digit nanomolar IC(50) values for CCR3.
authors.affiliation: Bristol-Myers Squibb Company, Experimental Station, PO Box 80336, Wilmington, DE 19880-0336, USA. dean.wacker@bms.com
authors.forename: Dean A
authors.initials: DA
authors.lastname: Wacker
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Santella
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Gardner
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Varnes
authors.forename: Melissa
authors.initials: M
authors.lastname: Estrella
authors.forename: George V
authors.initials: GV
authors.lastname: DeLucca
authors.forename: Soo S
authors.initials: SS
authors.lastname: Ko
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tanabe
authors.forename: Paul S
authors.initials: PS
authors.lastname: Watson
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Welch
authors.forename: Maryanne
authors.initials: M
authors.lastname: Covington
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Stowell
authors.forename: Eric A
authors.initials: EA
authors.lastname: Wadman
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Solomon
authors.forename: Robert C
authors.initials: RC
authors.lastname: Newton
authors.forename: George L
authors.initials: GL
authors.lastname: Trainor
authors.forename: Steven M
authors.initials: SM
authors.lastname: Friedman
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
authors.forename: John V
authors.initials: JV
authors.lastname: Duncia
mesh_terms: D000478:Alkylation; D000577:Amides / Q000737:chemistry / Q000378:metabolism; D018927:Anti-Asthmatic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D010880:Piperidines / Q000737:chemistry; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D018927:Anti-Asthmatic Agents; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D008024:Ligands; D010880:Piperidines; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D002118:Calcium