694499-26-8Relevant articles and documents
Insights into the modular design of kinase inhibitors and application to Abl and Axl
Johnson, Taylor K.,Lachacz, Eric J.,Lopez-Barcons, Lluis,Merajver, Sofia D.,Phadke, Sameer,Soellner, Matthew B.,Vandecan, Nathalie,Wu, Zhifen
supporting information, p. 64 - 71 (2022/02/26)
Scaffold hopping is a common strategy for generating kinase inhibitors that bind to the DFG-out inactive conformation. Small structural differences in inhibitor scaffolds can have significant effects on potency and selectivity across the kinome, however, these effects are often not studied in detail. Herein, we outline a design strategy to generate an array of DFG-out conformation inhibitors with three different hinge-binders and two DFG-pocket groups. We studied inhibitor selectivity across a large segment of the kinome and elucidated binding preferences that can be used in scaffold hopping campaigns. Using these analyses, we identified two selective inhibitors that display low nanomolar potency against Axl or wild-type and clinically relevant mutants of Abl.
KINASE INHIBITORS AND USES THEREOF
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, (2020/10/21)
This invention described herein relates to compounds of general formula (I) : (I), in which variable groups are as defined herein, and to their preparation and use. Uses for the compounds and for compositions containing them include treatment of cancer and other diseases mediated by protein kinases, such as Bcr-Abl kinase, and mutants thereof, such as the T315I mutant.
Alkynyl pyrimidine or alkynyl pyridine compound as well as composition and application thereof
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, (2020/08/18)
The invention relates to alkynyl pyrimidine or alkynyl pyridine compounds represented by a formula (I) or pharmaceutically acceptable salts, isomers, solvates, crystals or prodrugs thereof. The invention also discloses a pharmaceutical composition contain
Substituted diaryl amide compound as well as preparation method and application thereof
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, (2019/04/04)
The invention provides a substituted diaryl amide compound as well as a preparation method and application thereof. The substituted diaryl amide compound or a pharmaceutically acceptable salt thereofis of a structure of a formula [1] (the formula is shown
IRE1 SMALL MOLECULE INHIBITORS
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, (2018/06/22)
Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a
NOVEL INHIBITORS OF MAP4K1
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Page/Page column 67; 68, (2018/12/13)
The invention relates to novel inhibitors of MAP4K1 (HPK1) useful for the treatment of diseases or disorders characterised by dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. The inhibitors are of formula (I) wherein the definitions for A, D, E, F, R5, R6, R7, Z, ring Q, n, x and y are as given in the application.
Inhibitors to Overcome Secondary Mutations in the Stem Cell Factor Receptor KIT
Kaitsiotou, Helena,Keul, Marina,Hardick, Julia,Mühlenberg, Thomas,Ketzer, Julia,Ehrt, Christiane,Krüll, Jasmin,Medda, Federico,Koch, Oliver,Giordanetto, Fabrizio,Bauer, Sebastian,Rauh, Daniel
, p. 8801 - 8815 (2017/11/15)
In modern cancer therapy, the use of small organic molecules against receptor tyrosine kinases (RTKs) has been shown to be a valuable strategy. The association of cancer cells with dysregulated signaling pathways linked to RTKs represents a key element in
Design, synthesis and evaluation of derivatives based on pyrimidine scaffold as potent Pan-Raf inhibitors to overcome resistance
Wang, Lu,Zhang, Qing,Zhu, Gaoyuan,Zhang, Zhimin,Zhi, Yanle,Zhang, Li,Mao, Tianxiao,Zhou, Xiang,Chen, Yadong,Lu, Tao,Tang, Weifang
, p. 86 - 106 (2017/03/02)
Simutaneous targeting all Raf isoforms offers the prospect of enhanced efficacy as well as reduced potential for resistance. Described herein is the discovery and characterization of a series of pyrimidine scaffold with DFG-out conformation as potent Pan-Raf inhibitors. Among them, I-41 with excellent Pan-Raf potency demonstrates inhibitory activity against BRafWTphenotypic melanoma and BRafV600Ephenotypic colon cells. The western blot results for the Erk inhibition in human melanoma SK-Mel-2?cell lines showed I-41 inhibited the proliferation of SK-Mel-2?cell lines without paradoxical activation of Erk, which supported I-41 may become a good candidate compound to overcome the resistance of melanoma against the current BRafV600Einhibitor therapy. I-41 also have a favorable pharmacokinetic profile in rat. Synthesis, SAR, lead selection, and evaluation of the key compounds studies are described.
Preparation and application of triazole compound
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, (2017/07/22)
The invention provides preparation and application of a triazole compound. A preparation method comprises the following steps: enabling a first compound, namely 1-methyl-4-nitryl-2-(trifluoromethyl) benzene to react under the action of NBS, BPO and CCl4 s
3-ACETYLENYL-PYRAZOLE-PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND USES THEREOF
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, (2017/11/10)
The present invention relates to the field of chemical and medicine, more particularly, 3-ethynylpyrazolopyrimidine derivatives and their preparation methods and uses. The invention provides a 3-ethynylpyrazolopyrimidine derivative, and the structure is shown in formula I. The present invention also provides preparation methods and use of 3-ethynylpyrazolopyrimidine derivatives, comprising the compounds and derivatives, and their pharmaceutical compositions for the use of the treatment and prevention of tumors.
