The synthesis of a tritium, carbon-14, and stable isotope-labeled cathepsin C inhibitors
详细信息 查看全文
- 作者：Paul Allen ; Ryan A. Bragg ; Moya Caffrey ; Cecilia Ericsson ; Michael J. Hickey ; Lee P. Kingston and Charles S. Elmore
- 刊名：Journal of Labelled Compounds and Radiopharmaceuticals
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：60
- 期：2
- 页码：124-129
- 全文大小：601K
- ISSN：1099-1344
文摘
As part of a medicinal chemistry program aimed at developing a highly potent and selective cathepsin C inhibitor, tritium, carbon-14, and stable isotope-labeled materials were required. The synthesis of tritium-labeled methanesulfonate 5 was achieved via catalytic tritiolysis of a chloro precursor, albeit at a low radiochemical purity of 67%. Tritium-labeled AZD5248 was prepared via a 3-stage synthesis, utilizing amide-directed hydrogen isotope exchange. Carbon-14 and stable isotope-labeled AZD5248 were successfully prepared through modifications of the medicinal chemistry synthetic route, enabling the use of available labeled intermediates.