Background and overview of application examples of 2-fluoro-5-chloropyridine-4-boronic acid
2-Fluoro-5-chloropyridine-4-boronic acid is a boric acid derivative. Boric acid derivatives are widely used in organic synthesis for the formation of carbon-carbon bonds. In the Suzuki coupling, aryl halides and aryl or vinyl borates or boronic acids are coupled using Pd(PPh3)4.
Application examples of 2-fluoro-5-chloropyridine-4-boronic acid
[Formyl phenylboronic acid label: title] Application 1,
2-Fluoro-5-chloropyridine-4-boronic acid can be used to prepare phenylpyridinium compounds with the following structure. This compound is a HPK1 inhibitor. The main processes in which HPK1 participates in regulating TCR are (1) TCR binds to extracellular antigens through MHC, thereby activating the TCR pathway to transmit signals to downstream adapter protein molecules; (2) adapter protein tyrosine kinase Lck and Zap70 activate SLP76, and then Phosphorylated HPK1; (3) Activated HPK1 will then phosphorylate the receptor protein SLP-76; (4) The phosphorylation reaction of SLP-76 provides a variety of proteins for the 14-3-3 (TCR pathway inhibitory protein) receptor protein Binding site to form a complex; (5) The SLP-76 phosphorylated complex participates in the down-regulation of the Erk signaling pathway and is connected to the ubiquitination and degradation process of SLP76, resulting in a decrease in the TCR signaling pathway and T cell proliferation. In summary, HPK1 can negatively regulate the TCR signaling pathway. Therefore, HPK1 can be used as a new regulatory mechanism for T cell-mediated immune responses and become a new research and development hotspot for immune and anti-tumor.
Application examples of 2-fluoro-5-chloropyridine-4-boronic acid Application 2.
2-Fluoro-5-chloropyridine-4-boronic acid can be used to prepare CDK9 inhibitors with the following structure. Studies have found that abnormalities in the expression level or/and kinase activity of CDK9 can cause abnormalities in the expression of multiple proteins or/and their mRNA levels in cells. Among them, anti-apoptotic proteins such as Bcl-2, cell cycle-related regulatory proteins such as cyclin D1, p53 pathway-related proteins, certain proteins of the NF-κB pathway and those related to the tumor microenvironment have been confirmed and closely related to tumors. Proteins such as VEGF, etc. It can be said that CDK9 is one of the most critical molecules in the occurrence and development of tumors.
References
[1] From PCT Int. Appl., 2020193511, 01 Oct 2020
[2] [Invented in China, authorized by China Invention] CN201710257652.7 A novel inhibitor of cyclin-dependent kinase CDK9
