59717-96-3Relevant articles and documents
Design and synthesis of novel 1-substituted 3-(6-phenoxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine analogs as selective BTK inhibitors for the treatment of mantle cell lymphoma
Ran, Fansheng,Liu, Yang,Yu, Shengping,Guo, Kaiwen,Tang, Wendi,Chen, Xin,Zhao, Guisen
, (2019/11/11)
Ibrutinib (IBN), a first-in-class BTK-inhibitor, was approved by the FDA for the treatment of mantle cell lymphoma (MCL). Although IBN shows excellent performance as an anti-lymphoma agent, it has some undesirable side effects due to its off-target activities. Our studies yielded a novel series of 3-(6-phenoxypyridin-3-yl)-4-amine-1H-pyrazolo[3,4-d]pyrimidine derivatives capable of potent inhibition of Bruton's tyrosine kinase (BTK). Notably, compound 13e explained potent BTK inhibitory activity and could completely inhibit the phosphorylation of BTK and PLCγ2 in Z138 cells at low micromolar concentration. Compared with IBN, compound 13e improved anti-proliferative activities 3–40 folds in MCL cell lines with IC50 values lower than 1 μM. Low micromolar doses of 13e could induce strong cell apoptosis in Jeko-1 and Z138 cells. In addition, compound 13e showed greater BTK selectivity and higher stability in human liver microsomes than IBN and potential safety improvement for the treatment of MCL.
Reversible covalent Bruton's tyrosine kinase inhibitor, pharmaceutical composition and application thereof
-
Paragraph 0124-0127, (2019/12/02)
The invention discloses a reversible covalent Bruton's tyrosine kinase (BTK) inhibitor compound, a pharmaceutical composition and application of the compound and the pharmaceutical composition in preparation of drugs for treating diseases, disorders or symptoms benefitting from inhibition of Bruton's tyrosine kinase activity. The compound provided by the invention has strong in-vitro BTK kinase inhibition activity, and can be applied to treatment of diseases, disorders or symptoms, including B-cell lymphoma, autoimmune diseases, inflammatory diseases and the like, which benefit from inhibitionof Bruton's tyrosine kinase activity, alone or in combination with other drugs.
CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
-
Paragraph 0358, (2018/03/09)
Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.