Nankai University, State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin 300071, PR China.
Expert Opin Drug Discov. 2012 Jun;7(6):489-501. doi: 10.1517/17460441.2012.682725. Epub 2012 May 19.
The copper(I)-catalyzed 1,3-dipolar cycloaddition of alkynes and azides to form 1,2,3-triazoles is the most popular reaction in click chemistry. This reaction is also near-perfect, in terms of its robustness, due to the high degree of reliability and complete specificity. Furthermore, this reaction has been used increasingly in drug discovery, because the formed 1,2,3-triazole can act as both a bioisostere and a linker.
This review provides an overview of a most important click reaction, 1,3-dipolar cycloadditions of alkynes and azides, in the drug discovery.
Click chemistry is a very powerful tool, in the drug discovery, because it is very efficient in the creation of compound libraries through combinatorial methodology. However, the 1,2,3-triazole ring itself is not a commonly used pharmacophore and has rarely been found in marketed drugs, demonstrating that there are still some limitations during the use of 1,2,3-triazole in the molecules of drug candidates. Hopefully, in the next decade, we will witness the emergence of 1,2,3-triazole-bearing drugs on the market as this click reaction is used more and more widely in the drug discovery.
铜（I）催化的炔烃和叠氮化物的 1,3-偶极环加成反应形成 1,2,3-三唑是点击化学中最流行的反应。由于可靠性高和特异性完全，该反应也近乎完美。此外，该反应在药物发现中越来越多地被使用，因为形成的 1,2,3-三唑既可以作为生物等排体，也可以作为连接子。
本综述概述了药物发现中最重要的点击反应之一，即炔烃和叠氮化物的 1,3-偶极环加成反应。
点击化学是药物发现中非常强大的工具，因为它通过组合方法在化合物库的创建中非常高效。然而，1,2,3-三唑环本身并不是一个常用的药效团，在上市药物中很少发现，这表明在药物候选物的分子中使用 1,2,3-三唑仍然存在一些限制。希望在未来十年，随着点击反应在药物发现中越来越广泛地应用，我们将看到含有 1,2,3-三唑的药物在市场上的出现。
