Metal Catalyzed Dynamic Exchange Approach to 14-C Labeled Pharmaceuticals

14-C 标记药物的金属催化动态交换方法

• 批准号: 543917-2019
• 负责人: Arndtsen, Bruce
• 金额: $ 2.24万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=699709
• 关键词: Metal; Catalyzed; Dynamic; Exchange; Approach

This CRD proposal will support the research collaboration between Prof. Arndtsen at McGill University and Dr. Gauthier at Merck. The research is directed towards creating a more efficient method to generate carbon-14 radiolabeled pharmaceuticals. Radiolabeled drugs, and in particular those incorporating carbon-14, are required for all molecules in the clinical development. These labeled materials are used to track the drug's fate, toxicity, lifetime, and metabolism within the body. Such analyses are performed thoughout phase 1 through phase 3 clinical trials, and are necessary for the ultimate approval of drugs by regulatory agencies. The use of carbon-14 allows the drug structure to be labeled without changing its actual chemical structure, which is critical to avoid changing the behavior of the material. Unfortunately, the preparation of many carbon-14 labeled materials involves a long synthesis with radioactive material, limiting access to these materials in the timely fashion often needed by the pharmaceutical industry. The project here exploits two significant discoveries emerging from the Arndtsen (McGill) and Gauthier (Merck) groups in the past year, which demonstrate the ability of metal catalysts to mediate the exchange of covalent bonds in organic compounds. These will be used to develop a new and efficient new way to access carbon-14 radiolabeled drugs: via the direct exchange of carbon-14 into carboxylic acids on already prepared pharmaceutical candidates. Overall, the process would offer a versatile method to create carbon-14 labeled pharmaceuticals, and has significant potential for commercial impact in Merck's ability to clinically validate drugs.

该CRD提案将支持麦吉尔大学的Arbrossen教授和默克公司的Gauthier博士之间的研究合作。 该研究旨在创造一种更有效的方法来生产碳-14放射性标记的药物。 放射性标记的药物，特别是那些纳入碳-14，需要在临床开发的所有分子。 这些标记材料用于跟踪药物的命运，毒性，寿命和体内代谢。 这些分析在1期到3期临床试验中进行，并且对于监管机构最终批准药物是必要的。碳-14的使用允许在不改变其实际化学结构的情况下标记药物结构，这对于避免改变材料的行为至关重要。不幸的是，许多碳-14标记材料的制备涉及与放射性材料的长时间合成，限制了制药工业经常需要的及时获得这些材料。该项目利用了过去一年中阿克森（麦吉尔）和戈蒂埃（默克）团队的两项重大发现，这些发现证明了金属催化剂介导有机化合物中共价键交换的能力。 这些将被用于开发一种新的和有效的新方法来获得碳-14放射性标记的药物：通过碳-14直接交换成羧酸对已经制备的候选药物。 总的来说，该过程将提供一种多功能的方法来制造碳-14标记的药物，并对默克公司临床验证药物的能力产生重大的商业影响。