title: Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H₁ antagonists. Part I.
abstract: The discovery of potent small molecule dual antagonists of the human CCR3 and H(1) receptors is described for the treatment of allergic diseases, for example, asthma and allergic rhinitis. Optimizing in vitro potency and metabolic stability, starting from a CCR1 lead compound, led to compound 20 with potent dual CCR3/H(1) activity and in vitro metabolic stability.
authors.affiliation: AstraZeneca Respiratory & Inflammation iMED, Pepparedsleden 1, 431 83 Mölndal, Sweden. mark1.furber@astrazeneca.com
authors.forename: Mark
authors.initials: M
authors.lastname: Furber
authors.forename: Lilian
authors.initials: L
authors.lastname: Alcaraz
authors.forename: Christopher
authors.initials: C
authors.lastname: Luckhurst
authors.forename: Ash
authors.initials: A
authors.lastname: Bahl
authors.forename: Haydn
authors.initials: H
authors.lastname: Beaton
authors.forename: Keith
authors.initials: K
authors.lastname: Bowers
authors.forename: John
authors.initials: J
authors.lastname: Collington
authors.forename: Rebecca
authors.initials: R
authors.lastname: Denton
authors.forename: David
authors.initials: D
authors.lastname: Donald
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kinchin
authors.forename: Cathy
authors.initials: C
authors.lastname: MacDonald
authors.forename: Aaron
authors.initials: A
authors.lastname: Rigby
authors.forename: Rob
authors.initials: R
authors.lastname: Riley
authors.forename: Matt
authors.initials: M
authors.lastname: Soars
authors.forename: Brian
authors.initials: B
authors.lastname: Springthorpe
authors.forename: Peter
authors.initials: P
authors.lastname: Webborn
mesh_terms: D000818:Animals; D055808:Drug Discovery; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: C515350:CCR3 protein, human; D006877:Hydroxamic Acids; D010880:Piperidines; D054397:Receptors, CCR3; D011969:Receptors, Histamine H1