- Discovery of GNF-5837, a selective TRK inhibitor with efficacy in rodent cancer tumor models
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Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified. Optimization led to the identification of GNF-5837 (22), a potent, selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good tool for the elucidation of TRK biology in cancer and other nononcology indications.
- Albaugh, Pam,Fan, Yi,Mi, Yuan,Sun, Fangxian,Adrian, Francisco,Li, Nanxin,Jia, Yong,Sarkisova, Yelena,Kreusch, Andreas,Hood, Tami,Lu, Min,Liu, Guoxun,Huang, Shenlin,Liu, Zuosheng,Loren, Jon,Tuntland, Tove,Karanewsky, Donald S.,Seidel, H. Martin,Molteni, Valentina
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supporting information; experimental part
p. 140 - 145
(2012/04/10)
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- Indolin-2-one p38α inhibitors I: Design, profiling and crystallographic binding mode
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The use of structure-based design and molecular modeling led to the discovery of indolin-2-one derivatives as potent and selective p38α inhibitors. The predicted binding mode was confirmed by X-ray crystallography.
- Eastwood, Paul,González, Jacob,Gómez, Elena,Vidal, Bernat,Caturla, Francisco,Roca, Ramón,Balagué, Cristina,Orellana, Adelina,Domínguez, María
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scheme or table
p. 4130 - 4133
(2011/08/10)
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- New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors
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This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.
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Page/Page column 29
(2009/10/21)
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- New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors
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This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.
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Page/Page column 21
(2009/12/04)
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- Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof
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The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nACh receptors), activation of nACh receptors, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (e.g., indazoles and benzothiazoles), which act as ligands for the α7 nACh receptor subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 72
(2010/11/26)
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- COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
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The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly di
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Page/Page column 48
(2010/11/30)
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- Synthesis and biological evaluation of 3-ethylidene-1,3-dihydro-indol-2- ones as novel checkpoint 1 inhibitors
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Chk1 inhibitors have emerged as a novel class of neoplastic agents for abrogating the G2 DNA damage checkpoint arrest. Analogs of the Chk1 inhibitor, 3-ethylidene-1,3-dihydro-indol-2-one, were synthesized and tested in vitro for their inhibitory activitie
- Lin, Nan-Horng,Xia, Ping,Kovar, Peter,Park, Chang,Chen, Zehan,Zhang, Haiying,Rosenberg, Saul H.,Sham, Hing L.
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p. 421 - 426
(2007/10/03)
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- INDOLES, 1H-INDAZOLES, 1,2-BENZISOXAZOLES, AND 1,2-BENZISOTHIAZOLES, AND PREPARATION AND USES THEREOF
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The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nAChR), activation of nAChRs, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds for example, indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, which act as ligands for the α7 nAChR subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 44
(2008/06/13)
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- Hexahydro-cyclohepta-pyrrole oxindole as potent kinase inhibitors
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The present invention is directed to a class indolinone compounds, hexahydro-cyclohepta-pyrrole oxindoles, which are useful as protein kinase inhibitors.
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Page/Page column 23
(2010/02/08)
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- Novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole compounds
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Certain 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indoles are 5-HT ligands and are useful for treating diseases wherein modulation of 5-HT activity is desired.
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- 3-heteroarylidene-2-indolinone protein kinase inhibitors
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The present invention relates to novel 3-heteroarylidene-2-indolinone compounds and physiologically acceptable salts thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
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- Pyrrole substituted 2-indolinone protein kinase inhibitors
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The present invention relates to novel pyrrole substituted 2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
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- 3-(cycloalkanoheteroarylidenyl)-2-indolinone protein tyrosine kinase inhibitors
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The present invention relates to novel 3-(cycloalkano-heteroarylidenyl)-2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.
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Page column 29
(2010/02/05)
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- Benzylidene-1,3-dihydro-indol-2-one derivatives a receptor tyrosine kinase inhibitors, particularly of Raf kinases
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Compounds of general formula (I) wherein: R1is H or optionally joined with R2to form a fused ring selected from the group consisting of five to ten membered aryl, heteroaryl or heterocyclyl rings, R2and R3are in
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- 3-(cycloalkanoheteroarylidenyl)-2- indolinone protein tyrosine kinase inhibitors
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The present invention relates to novel 3-(cycloalkanoheteroarylidenyl)-2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.
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- Synthesis and some reactions of 6-bromooxindole
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An efficient synthesis of 4- and 6-bromooxindoles, previously unknown compounds, from 6- and 4-amino-2-nitrotoluenes and the transformation of 6-bromooxindole to 3-acylated derivatives are described.
- Kosuge,Ishida,Inaba,Nukaya
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p. 1414 - 1418
(2007/10/02)
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