948571-47-9Relevant articles and documents
FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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Paragraph 0236, (2021/04/02)
The present disclosure relates to a class of fused pyrimidine compounds of Formula I, their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to a process of preparation of these fused pyrimidine compounds, and to pharmaceutical compositions containing them.
Novel 1H-pyrazolo[3,4-d]pyrimidin-6-amino derivatives as potent selective Janus kinase 3 (JAK3) inhibitors. Evaluation of their improved effect for the treatment of rheumatoid arthritis
Chen, Cheng-Juan,Shu, Lei,Wang, Zhi-Jian,Yin, Yuan,Yu, Ru-Nan,Zhang, Da-Yong,Zhang, Tian-Tai
, (2020/03/17)
Selective JAK3 inhibitors have been shown to have a potential benefit in the treatment of autoimmune disorders. Here we report the identification of a series of pyrazolopyrimidine derivatives as potent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Most of these compounds (13k, 13n and 13 t), displayed stronger anti-JAK3 kinase activity and selectivity than tofacitinib. Furthermore, the most active inhibitor 13t (IC50 = 0.1 nM), also exhibited favourable selectivity for JAK3 in a panel of 9 kinases which contain the same cysteine. In a series of cytokinestimulated cellular analysis, compound 13 t, could potently block the JAK3-STAT signaling pathway. Further biological studies, including cellular antiproliferative activity assays and a rat adjuvant-induced arthritis model for in vivo evaluation, also indicated its efficacy and low toxicity in the treatment of rheumatoid arthritis. The results of these experimental explorations suggested that 13t is a promising lead compound for the development of selective JAK3 inhibitor with therapeutic potential in rheumatoid arthritis.
Preparation and application of novel 4,6-disubstituted aminopyrimidine JAK (janus kinase) inhibitor
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Paragraph 0202-0207; 0213-0217, (2019/05/08)
The invention discloses preparation and application of novel 4,6-disubstituted aminopyrimidine JAK (janus kinase) inhibitors, and provide drugs which can be used for preventing, treating and/or improving autoimmune diseases (for example, psoriasis, rheumatoid arthritis, inflammatory enteritis diseases, Jagren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus, etc.), and have excellent JAK inhibitory activity. The invention also provides pharmaceutically acceptable composition containing the compounds and methods for preparing the compounds.