884600-93-5Relevant articles and documents
Inhibitor of Bruton tyrosine kinase
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Paragraph 0140-0142, (2019/02/19)
The invention discloses a compound of a formula (I) with Btk inhibiting activity, wherein all variables are as defined in the description. The compound can be used for treating autoimmune diseases, heteroimmune diseases, cancers or thrombembolia. The inve
From Lead to Drug Candidate: Optimization of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as Agents for the Treatment of Triple Negative Breast Cancer
Zhang, Chun-Hui,Chen, Kai,Jiao, Yan,Li, Lin-Li,Li, Ya-Ping,Zhang, Rong-Jie,Zheng, Ming-Wu,Zhong, Lei,Huang, Shen-Zhen,Song, Chun-Li,Lin, Wan-Ting,Yang, Jiao,Xiang, Rong,Peng, Bing,Han, Jun-Hong,Lu, Guang-Wen,Wei, Yu-Quan,Yang, Sheng-Yong
supporting information, p. 9788 - 9805 (2016/11/19)
Herein we report the sophisticated process of structural optimization toward a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were synthesized. In vitro cell-based phenotypic screening together with in vivo assays and structure-activity relationship (SAR) studies finally led to the discovery of N-(3-((4-amino-1-(trans-4-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)ethynyl)-4-methylphenyl)-4-methyl-3-(trifluoromethyl)benzamide (13an). 13an is a multikinase inhibitor, which potently inhibited Src (IC50 = 0.003 μM), KDR (IC50 = 0.032 μM), and several kinases involved in the MAPK signal transduction. This compound showed potent anti-TNBC activities both in vitro and in vivo, and good pharmacokinetic properties and low toxicity. Mechanisms of action of anti-TNBC were also investigated. Collectively, the data obtained in this study indicate that 13an could be a promising drug candidate for the treatment of TNBC and hence merits further studies.
1H-1,8- NAPHTHYRIDIN-2ONES AS ANTI PROLIFERATIVE COMPOUNDS
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Page/Page column 36, (2015/12/30)
The present invention relates to novel antiproliferative1H-1, 8-naphthyridin-2-ones of the general formula (I) or pharmaceutically acceptable salts thereof: In which the variable groups are as defined herein, and their preparation and use in therapeutic treatment of disorders related to inhibition of tyrosine kinases in warm blooded animals. The compounds can overcome imatinib induced drug resistance.
DERIVATIVES OF 1 H-PYRAZOLO[3,4-B]PYRIDINE AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
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Paragraph 00271; 00355, (2015/03/13)
The present invention discloses compounds according to Formula (I): wherein R1, R2, R3, R4, L, and X are as defined herein. The present invention relates to compounds,methods for their production, pharmaceutical
Structure-guided design of aminopyrimidine amides as potent, selective inhibitors of lymphocyte specific kinase: Synthesis, structure-activity relationships, and inhibition of in vivo T cell activation
DiMauro, Erin F.,Newcomb, John,Nunes, Joseph J.,Bemis, Jean E.,Boucher, Christina,Chai, Lilly,Chaffee, Stuart C.,Deak, Holly L.,Epstein, Linda F.,Faust, Ted,Gallant, Paul,Gore, Anu,Gu, Yan,Henkle, Brad,Hsieh, Faye,Huang, Xin,Kim, Joseph L.,Lee, Josie H.,Martin, Matthew W.,McGowan, David C.,Metz, Daniela,Mohn, Deanna,Morgenstern, Kurt A.,Oliveira-Dos-Santos, Antonio,Patel, Vinod F.,Powers, David,Rose, Paul E.,Schneider, Stephen,Tomlinson, Susan A.,Tudor, Yan-Yan,Turci, Susan M.,Welcher, Andrew,Zhao, Huilin,Zhu, Li,Zhu, Xiaotian
, p. 1681 - 1694 (2008/12/20)
The lymphocyte-specific kinase (Lck), a member of the Src family of cytoplasmic tyrosine kinases, is expressed in T cells and natural killer (NK) cells. Genetic evidence, including knockout mice and human mutations, demonstrates that Lck kinase activity i
SUBSTITUTED HETEROCYCLES AS JANUS KINASE INHIBITORS
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Page/Page column 75, (2008/12/07)
The present invention provides substituted tricyclic heteroaryl compounds, including, for example, pyridoindoles, pyrimidinoindoles and triazinoindoles that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases such as immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.
Discovery of a potent and selective c-Kit inhibitor for the treatment of inflammatory diseases
Chen, Ning,Buerli, Roland W.,Neira, Susana,Hungate, Randall,Zhang, Dawei,Yu, Violeta,Nguyen, Yen,Tudor, Yanyan,Plant, Matthew,Flynn, Shaun,Meagher, Kristin L.,Lee, Matthew R.,Zhang, Xuxia,Itano, Andrea,Schrag, Michael,Xu, Yang,Ng, Gordon Y.,Hu, Essa
scheme or table, p. 4137 - 4141 (2009/05/26)
A potent and selective c-Kit inhibitor 20 was identified through a structure-activity relationship study. In an in vivo mouse model of mast cell activation, 20 blocked the SCF-induced histamine release with an EC50 of 26 nM.
Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of Tie-2 kinase
Cee, Victor J.,Albrecht, Brian K.,Geuns-Meyer, Stephanie,Hughes, Paul,Bellon, Steve,Bready, James,Caenepeel, Sean,Chaffee, Stuart C.,Coxon, Angela,Emery, Maurice,Fretland, Jenne,Gallant, Paul,Gu, Yan,Hodous, Brian L.,Hoffman, Doug,Johnson, Rebecca E.,Kendall, Richard,Kim, Joseph L.,Long, Alexander M.,McGowan, David,Morrison, Michael,Olivieri, Philip R.,Patel, Vinod F.,Polverino, Anthony,Powers, David,Rose, Paul,Wang, Ling,Zhao, Huilin
, p. 627 - 640 (2007/10/03)
The recognition that aberrant angiogenesis contributes to the pathology of inflammatory diseases, cancer, and myocardial ischemia has generated considerable interest in the molecular mechanisms that regulate blood vessel growth. The receptor tyrosine kinase Tie-2 is expressed primarily by vascular endothelial cells and is critical for embryonic vasculogenesis. Interference with the Tie-2 pathway by diverse blocking agents such as soluble Tie-2 receptors, anti-Tie-2 intrabodies, anti-Ang-2 antibodies, and peptide-F c conjugates has been shown to suppress tumor growth in xenograft studies. An alternative strategy for interfering with the Tie-2 signaling pathway involves direct inhibition of the kinase functions of the Tie-2 receptor. Herein we describe the development of alkynylpyrimidine amide derivatives as potent, selective, and orally available ATP-competitive inhibitors of Tie-2 autophosphorylation.
