A General Strategy for Site-Selective Incorporation of Deuterium and Tritium into Pyridines, Diazines, and Pharmaceuticals
A General Strategy for Site-Selective Incorporation of Deuterium and Tritium into Pyridines, Diazines, and Pharmaceuticals
复制标题
DOI：
10.1021/jacs.7b11710
复制
发表时间：
2018-02-14
影响因子：
15
通讯作者：
McNally, Andrew
中科院分区：
文献类型：
--
作者：
Koniarczyk, J. Luke;Hesk, David;McNally, Andrew
将氘和氚原子引入有机分子的方法对于药物化学是有价值的。吡啶类和二嗪类化合物在药物中的广泛应用意味着新的标记方法将为药物设计提供机会，并促进吸收、分布、代谢和排泄（ADME）研究。提出了一种广泛适用的方案，其中将吡啶、二嗪和药物转化为杂环鏻盐，然后进行同位素标记。同位素以高产率掺入，并且通常具有独特的区域选择性。
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.