Metal Catalyzed Dynamic Exchange Approach to 14-C Labeled Pharmaceuticals

这CRD提议将支持之间的科研合作Arndtsen教授麦吉尔大学博士在默克公司附近。这项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，特别是那些含有碳-14的药物，是临床开发中所有分子所必需的。这些标记的材料用于追踪药物的命运、毒性、寿命和体内代谢。这种分析在1期到3期临床试验期间进行，是监管机构最终批准药物的必要条件。碳14的使用允许标记药物结构实际而不改变其化学结构,这是至关重要的,以避免改变材料的行为。不幸的是，许多碳-14标记材料的制备涉及到与放射性物质的长时间合成，限制了制药工业经常需要的及时获得这些材料的途径。的新兴项目利用两个重要发现Arndtsen(麦吉尔)和附近(默克公司)集团在过去的一年中,这证明了金属催化剂的调解能力共价键的交换在有机化合物。这些将用于开发一种新的和有效的新方法来获取碳-14放射性标记的药物：通过将碳-14直接交换为已制备的候选药物上的羧酸。总的来说，该过程将提供一种通用的方法来制造碳-14标记的药物，并且对默克公司临床验证药物的能力具有重大的商业影响。

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.