- Novel quinazoline-containing compound, and intermediate and application thereof
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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.
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Paragraph 0142; 0144; 0147
(2021/06/12)
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- 3-Trinitromethyl-4-nitro-5-nitramine-1: H-pyrazole: A high energy density oxidizer
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A novel oxygen-rich energetic compound, 3-trinitromethyl-4-nitro-5-nitramine-1H-pyrazole (5), was obtained by one-step nitration of 2-(3-amino-1H-pyrazol-5-yl)acetic acid (4). Compound 5 was characterized by IR and NMR spectroscopy, elemental analysis and differential scanning calorimetry (DSC). Additionally, the structure of compound 5 was further confirmed by X-ray crystallography. Compound 5 has a high density (1.90 g cm-3), positive heat of formation (0.99 kJ g-1) and positive oxygen balance (24.8%). The calculated detonation velocity (D = 9124 m s-1) and pressure (P = 37.2 GPa) are superior to those of RDX (D = 8795 m s-1, P = 34.9 GPa). The calculated specific impulse of compound 5 (262 s) is higher than that of AP (157 s) and ADN (202 s). The combination of these attractive properties makes it a promising high energy density oxidizer.
- Xiong, Hualin,Yang, Hongwei,Cheng, Guangbin
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p. 13827 - 13831
(2019/09/18)
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- TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
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The present invention comprises inter alia compounds as shown in formula (I) or a pharmaceutically acceptable salt thereof.
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Page/Page column 124
(2010/12/29)
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- AURORA KINASE INHIBITORS
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Disclosed herein are Aurora kinase Inhibitors represented by Structural Formula (I): Values for the variables in Structural Formula (I) are defined herein.
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Page/Page column 47
(2009/10/22)
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- Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase
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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.
- 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
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p. 2213 - 2224
(2008/02/02)
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- PHOSPHONOOXY QUINAZOLINE DERIVATIVES AND THEIR PHARMACEUTICAL USE
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Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a nitrogen atom and one or two further nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.
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