Design, Synthesis, and Molecular Docking Study of Flavonol Derivatives as Selective JAK1 Inhibitors

摘要

The Janus kinase family members of intracellular nonreceptor tyrosine kinases (JAK1, JAK2, JAK3 and TYK2) play key roles in transmitting inflammatory and proliferative signals through the JAK-STAT (signal transducer and activator of transcription) pathway. Thus, the JAK kinases have been highlighted as targets of therapeutic intervention for cancer as well as inflammatory diseases. Among the JAK isozymes, JAK1 has been investigated as an attractive target for the treatment of immunologic disorders such as rheumatoid arthritis (RA). Several JAK1 inhibitors have been discovered as potential therapeutic agents for treatment of RA, but selective inhibition of JAK1 over other JAK isozymes needs to be achieved to provide efficacy against RA and to minimize side effects.