1349151-81-0Relevant articles and documents
Rational Design of 5-(4-(Isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine (VX-970, M6620): Optimization of Intra- and Intermolecular Polar Interactions of a New Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase Inhibitor
Knegtel, Ronald,Charrier, Jean-Damien,Durrant, Steven,Davis, Chris,O'Donnell, Michael,Storck, Pierre,Maccormick, Somhairle,Kay, David,Pinder, Joanne,Virani, Anisa,Twin, Heather,Griffiths, Matthew,Reaper, Philip,Littlewood, Peter,Young, Steve,Golec, Julian,Pollard, John
supporting information, p. 5547 - 5561 (2019/06/21)
The DNA damage response (DDR) is a DNA damage surveillance and repair mechanism that can limit the effectiveness of radiotherapy and DNA-damaging chemotherapy, commonly used treatment modalities in cancer. Two related kinases, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related kinase (ATR), work together as apical proteins in the DDR to maintain genome stability and cell survival in the face of potentially lethal forms of DNA damage. However, compromised ATM signaling is a common characteristic of tumor cells, which places greater reliance on ATR to mediate the DDR. In such circumstances, ATR inhibition has been shown to enhance the toxicity of DNA damaging chemotherapy to many cancer cells in multiple preclinical studies, while healthy tissue with functional ATM can tolerate ATR inhibition. ATR therefore represents a very attractive anticancer target. Herein we describe the discovery of VX-970/M6620, the first ATR inhibitor to enter clinical studies, which is based on a 2-aminopyrazine core first reported by Charrier et al. (J. Med. Chem. 2011, 54, 2320-2330, DOI: 10.1021/jm101488z).
COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
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Page/Page column 54-55, (2013/02/28)
The present invention relates to pyrrolopyrazines compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I wherein the variables are as defined herein
COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
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Page/Page column 42, (2011/12/02)
The present invention relates to pyrazine and pyridine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various dis
