Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds.
Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds.
复制标题
DOI：
10.1002/cmdc.202100641
复制
发表时间：
2022-04-05
期刊：
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
五氟磺酰（‐SF5）官能团作为一种生物异构体在药物化学中越来越受到关注。利用一系列基于溶液和无溶剂的方法，包括微波和球磨机技术，合成了含SF5的化合物库，包括酰胺、异恶唑和氧吲哚衍生物。该文库的检测靶标包括人二氢羟酸脱氢酶（HDHODH）。随后的重点方法是合成临床使用的疾病修饰抗风湿药物（DMARDs） Teriflunomide和来氟米特的类似物，考虑用于潜在的COVID - 19，其中SF5生物同位体部署导致与母体药物相比，HDHODH的抑制得到改善。结果表明SF5基团在药物化学中的应用。已制成一系列含有五氟磺胺基的分子，并与已知的类药物实体进行了测试。SF5官能团作为一种生物异构体在药物化学中越来越受到关注。该文库对包括人二氢乙酸脱氢酶（HDHODH）在内的靶标进行了检测。随后的重点方法导致Teriflunomide和来氟米特的类似物被考虑用于潜在的COVID - 19治疗，其中SF5生物同位体部署导致HDHODH对母体药物的抑制改善。
The pentafluorosulfanyl (‐SF5) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF5‐containing compounds, including amide, isoxazole, and oxindole derivatives, was synthesised using a range of solution‐based and solventless methods, including microwave and ball‐mill techniques. The library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to synthesis of analogues of the clinically used disease modifying anti‐rheumatic drugs (DMARDs), Teriflunomide and Leflunomide, considered for potential COVID‐19 use, where SF5 bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF5 group in medicinal chemistry. A range of molecules containing a pentafluorosulfanyl group have been made and tested versus known drug‐like entities. The SF5 functional group is of increasing interest as a bioisostere in medicinal chemistry. This library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to analogues of Teriflunomide and Leflunomide, considered for potential COVID‐19 treatment, where SF5 bioisostere deployment led to improved inhibition of HDHODH over the parent drugs.
登录
查看更多内容
影响因子：
4.9
作者：
Xu, Chunping;De, Sudipta;Luque, Rafael
通讯作者：
Luque, Rafael
影响因子：
3.2
作者：
Sansook S;Ocasio CA;Day IJ;Tizzard GJ;Coles SJ;Fedorov O;Bennett JM;Elkins JM;Spencer J
通讯作者：
Spencer J
影响因子：
11.4
作者：
Christian, Sven;Merz, Claudia;Janzer, Andreas
通讯作者：
Janzer, Andreas
DOI：
10.1016/s0969-2126(00)00077-0
发表时间：
2000-01-15
期刊：
STRUCTURE WITH FOLDING & DESIGN
影响因子：
--
作者：
Liu, SP;Neidhardt, EA;Clardy, J
通讯作者：
Clardy, J
影响因子：
5.5
作者：
Hu, Ke;Wang, Mengmei;Lan, Ke
通讯作者：
Lan, Ke