870959-50-5Relevant academic research and scientific papers
Bis-Quinazoline Derivatives as Inhibitors for Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase
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Paragraph 0120; 0121, (2013/11/19)
Novel bis-quinazoline derivatives as tyrosine kinase inhibitors, synthesis of these compounds, and novel methods for treating tyrosine kinase mediated diseases or disorders using these compounds are disclosed. In particular, the present invention provides
2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2
Wissner, Allan,Floyd, M. Brawner,Johnson, Bernard D.,Fraser, Heidi,Ingalls, Charles,Nittoli, Thomas,Dushin, Russell G.,Discafani, Carolyn,Nilakantan, Ramaswamy,Marini, Joseph,Ravi, Malini,Cheung, Kinwang,Tan, Xingzhi,Musto, Sylvia,Annable, Tami,Siegel, Marshall M.,Loganzo, Frank
, p. 7560 - 7581 (2007/10/03)
A series of 2-(quinazolin-4-ylamino)-[1,4] benzoquinone derivatives that function as potent covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2 (VEGFR-2) has been prepared by eerie ammonium nitrate oxidation of substituted (2,5- dimethoxyphenyl)(6,7-disubstituted-quinazolin-4-yl)amines and by displacement of the chlorine atom of substituted 2-chloro-5-(6,7-disubstituted-quinazolin-4- ylamino)[1,4]benzoquinones with various amines, anilines, phenols, and alcohols. Enzyme studies were conducted in the absence and presence of glutathione and plasma. Several of the compounds inhibit VEGF-stimulated autophosphorylation in intact cells. Kinetic experiments were performed to study the reactivity of selected inhibitors toward glutathione. Reactivities correlated with LUMO energies calculated as averages of those of individual conformers weighted by the Boltzmann distribution. These results and molecular modeling were used to rationalize the biological observations. The compounds behave as non-ATP-competitive inhibitors. Unequivocal evidence, from mass spectral studies, indicates that these inhibitors form a covalent interaction with Cys-1045. One member of this series displays antitumor activity in an in vivo model.
QUINONE SUBSTITUTED QUINAZOLINE AND QUINOLINE KINASE INHIBITORS
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Page/Page column 70, (2010/02/14)
The present invention provides for compounds with the general formula: A compound of formula (1) having the structure (1) wherein Z is a radical selected from the group (a), (b), or (c) as well as methods and compositions containing these compounds useful
