title: Syntheses of a radiolabelled CXCR2 antagonist AZD5069 and its major human metabolite.
abstract: The CXCR2 antagonist AZD5069 has been synthesized in tritium and carbon-14-labelled forms. [(3) H]AZD5069 was prepared via reductive dehalogenation of an iodinated precursor with tritium gas to provide material with a specific activity of 25.1 Ci/mmol. [(14) C]AZD5069 was labelled in the pyrimidine ring from [(14) C]thiourea in an overall radiochemical yield of 18%. In addition, a synthetic route to the major metabolite of AZD5069 was developed. The synthesis of this metabolite was achieved from AZD5069 using a chemoselective Lindgren-Pinnick reaction in order to minimize oxidation of the sulphide group.
authors.affiliation: Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, UK. michael.j.hickey@astrazeneca.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hickey
authors.affiliation: Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, UK.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Allen
authors.affiliation: Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Moya
authors.initials: M
authors.lastname: Caffrey
authors.affiliation: Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Hansen
authors.affiliation: Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Lee P
authors.initials: LP
authors.lastname: Kingston
authors.affiliation: Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilkinson
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007553:Isotope Labeling; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011854:Radiochemistry; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium / Q000737:chemistry
chemical_list: D002250:Carbon Radioisotopes; C000597960:N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide; D011743:Pyrimidines; D023063:Receptors, Interleukin-8B; D013449:Sulfonamides; D014316:Tritium
keywords: AZD5069; Lindgren-Pinnick; carbon-14; tritium