Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
Department of Process Research & Development, MRL, Merck Sharp & Dohme Corp. , Rahway, New Jersey 07065, United States.
J Am Chem Soc. 2018 Feb 14;140(6):1990-1993. doi: 10.1021/jacs.7b11710. Epub 2018 Feb 5.
Methods to incorporate deuterium and tritium atoms into organic molecules are valuable for medicinal chemistry. The prevalence of pyridines and diazines in pharmaceuticals means that new ways to label these heterocycles will present opportunities in drug design and facilitate absorption, distribution, metabolism, and excretion (ADME) studies. A broadly applicable protocol is presented wherein pyridines, diazines, and pharmaceuticals are converted into heterocyclic phosphonium salts and then isotopically labeled. The isotopes are incorporated in high yields and, in general, with exclusive regioselectivity.
将氘和氚原子掺入有机分子的方法对药物化学很有价值。吡啶和哒嗪在药物中的普遍存在意味着，标记这些杂环的新方法将为药物设计带来机遇，并促进吸收、分布、代谢和排泄（ADME）研究。本文提出了一种广泛适用的方案，其中将吡啶、哒嗪和药物转化为杂环鏻盐，然后进行同位素标记。这些同位素以高收率且通常具有专一地进行掺入。
