700-31-2Relevant academic research and scientific papers
SELECTIVE JAK2 INHIBITOR AND APPLICATION THEREOF
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Page/Page column 0076; 0077; 0185-1086, (2021/02/25)
Provided is a selective JAK2 inhibitor and application thereof. In particular, it relates to the compound of the following Formula (I), and the use of the compound in the treatment of JAK2-mediated related diseases and in the preparation of the medicament for treating JAK2-mediated related diseases.
Discovery and optimization of 2-aminopyridine derivatives as novel and selective JAK2 inhibitors
Ma, Xiangyu,Diao, Yanyan,Ge, Huan,Xu, Fangling,Zhu, Lili,Zhao, Zhenjiang,Li, Honglin
supporting information, (2020/03/05)
Janus kinases (JAKs) including JAK1, JAK2, JAK3, and TYK2 are members of a family of intracellular nonreceptor tyrosine kinases, which have been demonstrated to be critical in the cell signaling pathway and involved in inflammatory diseases and cancer. V617F mutation in JAK2 has been implicated in polycythaemia vera (PV), essential thrombocythaemia (ET) and myelofibrosis (MF). Here, we described the design, synthesis, and biological evaluation of a series of 2-aminopyridine derivatives. The results of enzymatic activity assays supported compound 16m-(R) as a potential and selective JAK2 inhibitor, which exhibited high inhibitory activity with an IC50 of 3 nM against JAK2, and 85- and 76-fold selectivity over JAK1 and JAK3, respectively. Structure-activity relationships (SAR) and mechanistic analysis demonstrated that 16m-(R) might be a promising selective JAK2 inhibitor for further study.
Design, synthesis and structure-activity relationship study of aminopyridine derivatives as novel inhibitors of Janus kinase 2
Wang, Wanqi,Diao, Yanyan,Li, Wenjie,Luo, Yating,Yang, Tingyuan,Zhao, Yuyu,Qi, TianTian,Xu, Fangling,Ma, Xiangyu,Ge, Huan,Liang, Yingfan,Zhao, Zhenjiang,Liang, Xin,Wang, Rui,Zhu, Lili,Li, Honglin,Xu, Yufang
supporting information, p. 1507 - 1513 (2019/04/17)
Janus Kinase 2 (JAK2) is a kind of intracellular non-receptor protein tyrosine kinase and has been certified as an important target for the treatment of myeloproliferative neoplasms and rheumatoid arthritis. However, the low selectivity and potential safety issues restrict the clinical applications of JAK2 inhibitors. Here we found that crizotinib showed good inhibitory activity against JAK2 by enzymatic assays (IC50 = 27 nM). Then we carried out structure-based drug design and synthesized a series of compounds with an aminopyridine scaffold. Finally, compound 12k and 12l were identified as the promising inhibitors of JAK2, which exhibited high inhibitory activity (IC50 = 6 nM and 3 nM, respectively) and selectivity for JAK2 over JAK1 and JAK3, and showed potent antiproliferative activities toward HEL human erythroleukemia cells. Moreover, 12k suppressed symptoms of the collagen-induced arthritis (CIA) model in rats.
Novel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases
Steinig, Arno G.,Li, An-Hu,Wang, Jing,Chen, Xin,Dong, Hanqing,Ferraro, Caterina,Jin, Meizhong,Kadalbajoo, Mridula,Kleinberg, Andrew,Stolz, Kathryn M.,Tavares-Greco, Paula A.,Wang, Ti,Albertella, Mark R.,Peng, Yue,Crew, Linda,Kahler, Jennifer,Kan, Julie,Schulz, Ryan,Cooke, Andy,Bittner, Mark,Turton, Roy W.,Franklin, Maryland,Gokhale, Prafulla,Landfair, Darla,Mantis, Christine,Workman, Jen,Wild, Robert,Pachter, Jonathan,Epstein, David,Mulvihill, Mark J.
, p. 4381 - 4387 (2013/07/26)
A series of novel 6-aminofuro[3,2-c]pyridines as kinase inhibitors is described, most notably, OSI-296 (6). We discuss our exploration of structure-activity relationships and optimization leading to OSI-296 and disclose its pharmacological activity against cMET and RON in cellular assays. OSI-296 is a potent and selective inhibitor of cMET and RON kinases that shows in vivo efficacy in tumor xenografts models upon oral dosing and is well tolerated.
