Yang, Tao; Hu, Mengshi; Chen, Yong; Xiang, Mingli; Tang, Minghai; Qi, Wenyan; Shi, Mingsong; He, Jun; Yuan, Xue; Zhang, Chufeng; Liu, Kongjun; Li, Jiewen; Yang, Zhuang; Chen, Lijuan published their research in Journal of Medicinal Chemistry on December 10 ,2020. The article was titled 《N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms》.Related Products of 186390-79-4 The article contains the following contents:
In this study, we described a series of N-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective JAK2 (Janus kinase 2) inhibitors. Systematic exploration of the structure-activity relationship though cyclization modification based on previously reported compound 18e led to the discovery of the superior derivative 13ac. Compound 13ac showed excellent potency on JAK2 kinase, SET-2, and Ba/F3V617F cells (high expression of JAK2V617F mutation) with IC50 values of 3, 11.7, and 41 nM, resp. Further mechanistic studies demonstrated that compound 13ac could downregulate the phosphorylation of downstream proteins of JAK2 kinase in cells. Compound 13ac also showed good selectivity in kinase scanning and potent in vivo antitumor efficacy with 82.3% tumor growth inhibition in the SET-2 xenograft model. Moreover, 13ac significantly ameliorated the disease symptoms in a Ba/F3-JAK2V617F allograft model, with 77.1% normalization of spleen weight, which was more potent than Ruxolitinib. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl 6-nitro-3,4-dihydroisoquinoline-2(1H)-carboxylate(cas: 186390-79-4Related Products of 186390-79-4)
tert-Butyl 6-nitro-3,4-dihydroisoquinoline-2(1H)-carboxylate(cas: 186390-79-4) belongs to isoquinoline.Related Products of 186390-79-4 Isoquinoline is a structural isomer of quinoline, and quinoline derivatives are fused ring compounds of pyridine and benzene rings, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem