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Syntheses of a radiolabelled CXCR2 antagonist AZD5069 and its major human metabolite |
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| Authors: | Michael J. Hickey Paul H. Allen Moya Caffrey Peter Hansen Lee P. Kingston David J. Wilkinson |
| Affiliation: | 1. Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, UK;2. Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden;3. Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden |
| Abstract: | The CXCR2 antagonist AZD5069 has been synthesized in tritium and carbon‐14‐labelled forms. [3H]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. [14C]AZD5069 was labelled in the pyrimidine ring from [14C]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. |
| Keywords: | carbon‐14 tritium AZD5069 Lindgren– Pinnick |