The synthesis of [14C]AZD5122. Incorporation of an IV 14C-microtracer dose into a first in human study to determine the absolute oral bioavailability of AZD5122

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• 作者：Michael J. Hickey ; Paul H. Allen ; Lee P. Kingston and David J. Wilkinson
• 刊名：Journal of Labelled Compounds and Radiopharmaceuticals
• 出版年：2016
• 出版时间：30 May 2016
• 年：2016
• 卷：59
• 期：6
• 页码：245-249
• 全文大小：400K
• ISSN：1099-1344

文摘

AZD5122, N-(2-(2,3-difluorobenzylthio)-6-((2R,3R)-3,4-dihydroxybutan-2-ylamino)pyrimidin-4-yl)azetidine-1-sulfonamide was under investigation as a potential chemokine receptor CXCR2 antagonist for the treatment for inflammatory diseases. To gain a better understanding of the human pharmacokinetic profile, an exploratory phase I IV microtracer study was conducted using carbon-14 radiolabelled AZD5122. [¹⁴C]AZD5122 was carbon-14 labelled in the pyrimidine ring in five steps in an overall radiochemical yield of 19% from [¹⁴C]thiourea. The absolute oral bioavailability of AZD5122 was assessed in healthy subjects by an oral administration of AZD5122, followed by a concomitant intravenous [¹⁴C]AZD5122 microdose.