Keuler Tim, Ferber Dominic, Marleaux Michael, Geyer Matthias, Gütschow Michael
Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.
Institute of Structural Biology, University of Bonn, 53127 Bonn, Germany.
ACS Omega. 2022 Feb 23;7(9):8158-8162. doi: 10.1021/acsomega.2c00125. eCollection 2022 Mar 8.
In recent drug development efforts, particular emphasis has been devoted to the chemical interference with the NLRP3 inflammasome. A series of 12 tailored sulfonylureas was designed, prepared through convergent syntheses with a final sodium hydride-promoted reaction of isocyanates and sulfonamides, and subjected to a systematic, high-performance liquid chromatography-based survey of the chemical stability, a critical issue of sulfonylureas in terms of preparation, storage, and application. NLRP3 binding was determined by surface plasmon resonance spectroscopy. Sulfonylurea was identified to be equipotent and similarly stable compared to the prototypical NLRP3 inhibitor MCC950.
在最近的药物研发工作中，特别强调了对NLRP3炎性小体的化学干扰。设计了一系列12种定制的磺脲类化合物，通过汇聚合成法制备，最终通过异氰酸酯和磺酰胺在氢化钠促进下的反应得到，并对其化学稳定性进行了系统的基于高效液相色谱的研究，这是磺脲类化合物在制备、储存和应用方面的一个关键问题。通过表面等离子体共振光谱法测定NLRP3结合情况。与典型的NLRP3抑制剂MCC950相比，磺脲类化合物被鉴定为具有同等效力且稳定性相似。
