6608-47-5Relevant articles and documents
FGFR4 Inhibitor. Compositions and their use in pharmaceutical preparations
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Paragraph 0088-0091, (2021/10/27)
The invention provides 3 inhibitor which takes 4 - 4 dihydropyrimidine [5 - d,2] pyrimidine - (1H) FGFR4 ketone as a mother nucleus and has a covalent structure. The examples give 9 specific compounds and kinase inhibitory activity testing of these 9 compounds, wherein LX08 for FGFR4 kinase inhibitory activity is only 7 nm, lower than FIIN - 2 of the active control, and potential application prospects. In addition, by subjecting the synthesized compound to MALDI-TOF mass spectrometry, we found that compounds of LX01, LX05, LX06, LX07, LX08 are covalently bound to FGFR4 of Cys552, cannot covalently bind FGFR4 of Cys477, and LX09 are FGFR4 inhibitors which can be covalently bound to the two cysteines Cys552 and Cys477 in FGFR4.
Structure-Based Design of Selective, Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors
Rowlands, Rachel A.,Cato, M. Claire,Waldschmidt, Helen V.,Bouley, Renee A.,Chen, Qiuyan,Avramova, Larisa,Larsen, Scott D.,Tesmer, John J. G.,White, Andrew D.
supporting information, p. 1628 - 1634 (2019/12/03)
The ability of G protein-coupled receptor (GPCR) kinases (GRKs) to regulate desensitization of GPCRs has made GRK2 and GRK5 attractive targets for treating heart failure and other diseases such as cancer. Although advances have been made toward developing inhibitors that are selective for GRK2, there have been far fewer reports of GRK5 selective compounds. Herein, we describe the development of GRK5 subfamily selective inhibitors, 5 and 16d that covalently interact with a nonconserved cysteine (Cys474) unique to this subfamily. Compounds 5 and 16d feature a highly amenable pyrrolopyrimidine scaffold that affords high nanomolar to low micromolar activity that can be easily modified with Michael acceptors with various reactivities and geometries. Our work thereby establishes a new pathway toward further development of subfamily selective GRK inhibitors and establishes Cys474 as a new and useful covalent handle in GRK5 drug discovery.
A convenient synthesis of (E)-conjugated polyene sulfonyl derivatives with excellent stereospecificity
Yu, Chunyan,Lv, Zhongwen,Xu, Sheng,Zhang, Jun
supporting information, p. 3234 - 3237 (2018/07/25)
A highly selective synthesis of conjugated polyene sulfonyl derivatives is described via the elimination of disulfonyl chloride with readily accessible raw material dihaloalkane. The protocol offers a convenient way to form sulfonamides, sulfonates and even sulfones. Furthermore, this method was manipulated under mild condition with simple operation in high yield to afford only trans products.
