174891-10-2Relevant articles and documents
Novel quinazoline-containing compound, and intermediate and application thereof
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Paragraph 0142; 0144; 0147, (2021/06/12)
The present invention discloses a quinazoline-containing compound having the formula (IA), (IB) or (IC), or a pharmaceutically acceptable salt or a prodrug molecule thereof. The compound is suitable for use as an Aurora kinase inhibitor and is thus suitable for the treatment of Aurora-mediated diseases characterized by excessive or abnormal cell proliferation, for example, cancer.
TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
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Page/Page column 124, (2010/12/29)
The present invention comprises inter alia compounds as shown in formula (I) or a pharmaceutically acceptable salt thereof.
Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase
Mortlock, Andrew A.,Foote, Kevin M.,Heron, Nicola M.,Jung, Frédéric H.,Pasquet, Georges,Lohmann, Jean-Jacques M.,Warin, Nicolas,Renaud, Fabrice,De Savi, Chris,Roberts, Nicola J.,Johnson, Trevor,Dousson, Cyril B.,Hill, George B.,Perkins, David,Hatter, Glenn,Wilkinson, Robert W.,Wedge, Stephen R.,Heaton, Simon P.,Odedra, Rajesh,Keen, Nicholas J.,Crafter, Claire,Brown, Elaine,Thompson, Katherine,Brightwell, Stephen,Khatri, Liz,Brady, Madeleine C.,Kearney, Sarah,McKillop, David,Rhead, Steve,Parry, Tony,Green, Stephen
, p. 2213 - 2224 (2008/02/02)
The Aurora kinases have been the subject of considerable interest as targets for the development of new anticancer agents. While evidence suggests inhibition of Aurora B kinase gives rise to the more pronounced antiproliferative phenotype, the most clinically advanced agents reported to date typically inhibit both Aurora A and B. We have discovered a series of pyrazoloquinazolines, some of which show greater than 1000-fold selectivity for Aurora B over Aurora A kinase activity, in recombinant enzyme assays. These compounds have been designed for parenteral administration and achieve high levels of solubility by virtue of their ability to be delivered as readily activated phosphate derivatives. The prodrugs are comprehensively converted to the des-phosphate form in vivo, and the active species have advantageous pharmacokinetic properties and safety pharmacology profiles. The compounds display striking in vivo activity, and compound 5 (AZD1152) has been selected for clinical evaluation and is currently in phase 1 clinical trials.