- Pyrimidine hydrazone derivative and preparation method and application thereof
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The invention relates to pyrimidine hydrazone derivatives as shown in a chemical structural formula I or II, pharmaceutically acceptable salts and pharmaceutical compositions thereof, and an application of the pyrimidine hydrazone derivatives and the pharmaceutically acceptable salts and the pharmaceutical compositions in preparation of influenza virus neuraminidase inhibitors, wherein X is selected from: fluorine, chlorine, bromine, hydroxyl, dihydroxy, 2-hydroxy-3-methoxy, 2-hydroxy-4-methoxy, 2-hydroxy-5-C1-C2 alkoxy, 2-hydroxy-6-C1-C2 alkoxy, 3-hydroxy-2-C1-C2 alkoxy, 3-hydroxy-4-C1-C2 alkoxy, 3-hydroxy-5-methyl C1-C2 alkoxy , 3-hydroxy-6-C1-C2 alkoxy, 4-hydroxy-2-C1-C2 alkoxy, 4-hydroxy-3-C1-C2 alkoxy, 4-hydroxy-3, 5-diC1-C2 alkoxy, trihydroxy or 4-hydroxy-3,5-dimethyl; and Y is selected from: fluorine, chlorine, bromine, acetamido, hydroxyl or methoxy.
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Paragraph 0078-0079; 0083-0085
(2020/11/23)
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- Discovery of N-(4-(6-Acetamidopyrimidin-4-yloxy)phenyl)-2-(2-(trifluoromethyl)phenyl)acetamide (CHMFL-FLT3-335) as a Potent FMS-like Tyrosine Kinase 3 Internal Tandem Duplication (FLT3-ITD) Mutant Selective Inhibitor for Acute Myeloid Leukemia
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Most of the current FMS-like tyrosine kinase 3 (FLT3) inhibitors lack selectivity between FLT3 kinase and cKIT kinase as well as the FLT3 wt and internal tandem duplication (ITD) mutants. We report a new compound 27, which displays GI50 values of 30-80 nM against different ITD mutants and achieves selectivity over both FLT3 wt (8-fold) and cKIT kinase in the transformed BaF3 cells (>300-fold). 27 potently inhibits the proliferation of the FLT3-ITD-positive acute myeloid leukemia cancer lines through suppression of the phosphorylation of FLT3 kinase and downstream signaling pathways, induction of apoptosis, and arresting the cell cycle into the G0/G1 phase. 27 also displays potent antiproliferative effect against FLT3-ITD-positive patient primary cells, whereas it does not apparently affect FLT3 wt primary cells. In addition, it also exhibits a good therapeutic window to PBMC compared to PKC412. In the in vivo studies, 27 demonstrates favorable PK profiles and suppresses the tumor growth in the MV4-11 cell inoculated mouse xenograft model.
- Liang, Xiaofei,Wang, Beilei,Chen, Cheng,Wang, Aoli,Hu, Chen,Zou, Fengming,Yu, Kailin,Liu, Qingwang,Li, Feng,Hu, Zhenquan,Lu, Tingting,Wang, Junjie,Wang, Li,Weisberg, Ellen L.,Li, Lili,Xia, Ruixiang,Wang, Wenchao,Ren, Tao,Ge, Jian,Liu, Jing,Liu, Qingsong
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p. 875 - 892
(2019/01/21)
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- Novel pyrimidine derivative kinase inhibitor
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The invention relates to a kinase inhibitor comprising a compound of formula I or a pharmaceutically acceptable salt, solvate, ester, acid, metabolite or prodrug thereof. The invention also relates toa pharmaceutical composition comprising the kinase inhibitor, use of the compound and composition to inhibit wild type FLT3, mutant type FLT3-ITD, PDGFR[alpha] and/or PDGFR[beta] kinase activity in cells or subjects, and uses and methods for preventing or treating kinase-related disorders in the subjects.
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Paragraph 0235; 0236; 0237
(2018/09/08)
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- BIARYL KINASE INHIBITORS
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The present disclosure is directed to biaryl compounds of formula (I) which can inhibit AAKl (adaptor associated kinase 1), compositions comprising such compounds and their use for treating e.g. pain, Alzheimer's disease, Parkinson's disease and schizophrenia.
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Page/Page column 285; 286
(2017/05/07)
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- SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF
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This invention provides compounds of formula (I): wherein R1, R1b, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.
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Page/Page column 54
(2012/02/01)
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- HETEROBICYCLIC CARBOXAMIDES AS INHIBITORS FOR KINASES
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The invention relates to novel compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula (I) and to the use of a compound of formula (I) for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in particular tumour diseases.
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Page/Page column 52
(2010/11/28)
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- IDENTIFICATION OF KINASE INHIBITORS
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The invention concerns the identification of protein kinase inhibitors that preferentially bind to the inactive conformation of a target protein kinase. The inhibitors are identified by locking the target protein kinase in an inactive conformation, and us
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Page/Page column 69-70
(2008/06/13)
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