Bipiperidinyl carboxylic acid amides as potent, selective, and functionally active CCR4 antagonists.
A cell-based assay for the chemokine G-protein-coupled receptor CCR4 was developed, and used to screen a small-molecule compound collection in a multiplex format. A series of bipiperidinyl carboxylic acid amides amenable to parallel chemistry were derived that were potent and selective antagonists of CCR4. One prototype compound was shown to be active in a functional model of chemotaxis, making it a useful chemical tool to explore the role of CCR4 in asthma, allergy, diabetes, and cancer.
Kuhn
Cyrille F
CF
Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA. cyrille.f.kuhn@pfizer.com
Bazin
Marc
M
Philippe
Laurence
L
Zhang
Jiansu
J
Tylaska
Laurie
L
Miret
Juan
J
Bauer
Paul H
PH
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D001712:Biperiden / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D002264:Carboxylic Acids; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D001712:Biperiden