title: Scaffold-hopping with zwitterionic CCR3 antagonists: identification and optimisation of a series with good potency and pharmacokinetics leading to the discovery of AZ12436092.
abstract: The discovery and optimisation of a series of zwitterionic CCR3 antagonists is described. Optimisation of the structure led to AZ12436092, a compound with excellent selectivity over activity at hERG and outstanding pharmacokinetics in preclinical species.
authors.affiliation: Department of Bioscience, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, United Kingdom.
authors.forename: Ash
authors.initials: A
authors.lastname: Bahl
authors.forename: Patrick
authors.initials: P
authors.lastname: Barton
authors.forename: Keith
authors.initials: K
authors.lastname: Bowers
authors.forename: Moya V
authors.initials: MV
authors.lastname: Caffrey
authors.forename: Rebecca
authors.initials: R
authors.lastname: Denton
authors.forename: Peter
authors.initials: P
authors.lastname: Gilmour
authors.forename: Shaun
authors.initials: S
authors.lastname: Hawley
authors.forename: Tero
authors.initials: T
authors.lastname: Linannen
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Luckhurst
authors.forename: Tobias
authors.initials: T
authors.lastname: Mochel
authors.forename: Matthew W D
authors.initials: MW
authors.lastname: Perry
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Riley
authors.forename: Emma
authors.initials: E
authors.lastname: Roe
authors.forename: Brian
authors.initials: B
authors.lastname: Springthorpe
authors.forename: Linda
authors.initials: L
authors.lastname: Stein
authors.forename: Peter
authors.initials: P
authors.lastname: Webborn
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*
chemical_list: C579012:AZ12436092; D010880:Piperidines; D054397:Receptors, CCR3