Enamine, Ltd. , 78 Chervonotkatska Street , Kyiv , 02094 , Ukraine.
Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, Institute of Bioorganic Chemistry and Petrochemistry , National Academy of Sciences of Ukraine , Kyiv , 02094 , Ukraine.
ACS Comb Sci. 2018 Jul 9;20(7):461-466. doi: 10.1021/acscombsci.8b00060. Epub 2018 Jun 18.
A 1,2,4-triazole motif is present in numerous commercialized and investigational bioactive molecules. Despite its importance for medicinal chemistry, there is a lack of convenient combinatorial approaches toward this molecular core. Herein, we present a synthetic strategy suitable for the quick preparation of a library of structurally diverse 1,2,4-triazoles in a one-pot setting. The key steps include the formation of thioureas followed by S-alkylation using 1,3-propane sultone and consecutive ring closure leading to the desired 1,2,4-triazoles. Parallel synthesis yields thousands of 1,2,4-triazoles in a cost- and time-efficient manner from commercially available chemicals.
1,2,4-三唑基序存在于许多商业化和研究性的生物活性分子中。尽管它对药物化学很重要，但对于这种分子核心，缺乏方便的组合方法。在此，我们提出了一种适合于在一锅法中快速制备结构多样的 1,2,4-三唑文库的合成策略。关键步骤包括形成硫脲，然后用 1,3-丙烷砜进行 S-烷基化，然后连续环化得到所需的 1,2,4-三唑。平行合成可从商业可得的化学品中以经济高效的方式生成数千种 1,2,4-三唑。
