Syntheses of a radiolabelled CXCR2 antagonist AZD5069 and its major human metabolite. (27th July 2016)

• Record Type: Journal Article
• Authors: Hickey, Michael J.; Allen, Paul H.; Caffrey, Moya; Hansen, Peter; Kingston, Lee P.; Wilkinson, David J.
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 59:Number 11(2016)
• Page Start: 432
• Page End: 438
• Publication Date: 2016-07-27
• Subjects: carbon‐14 -- tritium -- AZD5069 -- Lindgren–Pinnick; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3429
• Languages: English
• ISSNs: 0362-4803

Abstract

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. Abstract : To support the clinical development of a CXCR2 antagonist, the syntheses of tritium and carbon‐14‐labelled AZD5069 are described. A chemoselective Lindgren–Pinnick oxidation to prepare AZD5069 acid metabolite is also presented.