title: Evaluation of a series of bicyclic CXCR2 antagonists.
abstract: The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists with markedly improved biological and pharmacokinetic properties, which are suitable pharmacological tools to probe the in vivo effects of CXCR2 antagonism combined with the associated CCR2 activity.
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, United Kingdom. iain.walters@astrazeneca.com
authors.forename: Iain
authors.initials: I
authors.lastname: Walters
authors.forename: Caroline
authors.initials: C
authors.lastname: Austin
authors.forename: Rupert
authors.initials: R
authors.lastname: Austin
authors.forename: Roger
authors.initials: R
authors.lastname: Bonnert
authors.forename: Peter
authors.initials: P
authors.lastname: Cage
authors.forename: Mark
authors.initials: M
authors.lastname: Christie
authors.forename: Mark
authors.initials: M
authors.lastname: Ebden
authors.forename: Stuart
authors.initials: S
authors.lastname: Gardiner
authors.forename: Caroline
authors.initials: C
authors.lastname: Grahames
authors.forename: Steven
authors.initials: S
authors.lastname: Hill
authors.forename: Fraser
authors.initials: F
authors.lastname: Hunt
authors.forename: Robert
authors.initials: R
authors.lastname: Jewell
authors.forename: Shirley
authors.initials: S
authors.lastname: Lewis
authors.forename: Iain
authors.initials: I
authors.lastname: Martin
authors.lastname: David Nicholls
authors.lastname: David Robinson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004353:Drug Evaluation, Preclinical; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines; D023063:Receptors, Interleukin-8B