- PYRROLO[2,1-F][1,2,4]TRIAZINE DERIVATIVES SERVING AS SELECTIVE HER2 INHIBITORS AND APPLICATION THEREOF
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The present invention relates to a group of pyrrolo[2, 1-f][1,2,4]triazine derivatives serving as selective HER2 inhibitors and an application thereof in the preparation of a drug that serves as an HER2 inhibitor. Specifically, the present invention relates to a compound represented by formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof.
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Paragraph 0113; 0115
(2021/03/18)
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- Bromine structural domain inhibitor compound and application thereof
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The invention relates to a bromine structural domain inhibitor and provides a compound shown in a general formula I, pharmaceutical salt, an enantiomer, a diastereoisomer, an atropisomer, racemate, apolymorphic substance and solvate of the compound or an isotope labelled compound (including a deuterium substituted compound), a preparation method of the compound, pharmaceutical composition containing the compound and an application of the above components in pharmaceuticals.
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Paragraph 0127-0128; 0131-0132
(2019/08/02)
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- PYRROLOTRIAZINE KINASE INHIBITORS
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 96
(2015/04/28)
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- Development of a practical synthesis of a functionalized pyrrolo[2,1-f][1,2,4]triazine nucleus
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Functionalized pyrrolotriazine 1b is a key heterocyclic building block in the synthesis of BMS-690514, a potent anticancer agent. Described herein are our development activities that led to the efficient preparation of 1b on a large scale. The key transformations include a selective C-alkylation of an oxalacetate salt with a hydrazonyl bromide to form a 2-hydrazonoethyl-3- oxosuccinate, followed by cyclodehydration to an aminopyrrole. Subsequent deprotection and condensation with formamidine afforded the pyrrolotriazine scaffold. Further elaboration of this core provided the desired pyrrolotriazinyl amine.
- Zheng, Bin,Conlon, David A.,Corbett, R. Michael,Chau, Melissa,Hsieh, Dau-Ming,Yeboah, Agnes,Hsieh, Daniel,Mueslehiddinoglu, Jale,Gallagher, William P.,Simon, Jeffrey N.,Burt, Justin
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p. 1846 - 1853
(2013/01/15)
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- Discovery of the pyrrolo[2,1-f][1,2,4]triazine nucleus as a new kinase inhibitor template
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The pyrrolo[2,1-f][1,2,4]triazine nucleus was identified as a novel kinase inhibitor template which effectively mimics the well-known quinazoline kinase inhibitor scaffold. Attachment of a 4-((3-chloro-4-fluorophenyl)amino) substituent to the template provided potent biochemical inhibitors of the tyrosine kinase activity of EGFR, as well as inhibition of cellular proliferation of the human colon tumor cell line DiFi. Attachment of a 4-((3-hydroxy-4-methylphenyl)amino) substituent provided potent inhibitors of VEGFR-2 which also showed effects on the VEGF-dependent proliferation of human umbilical vein endothelial cells. Biological activity was maintained with substitution at positions 5 or 6, but not 7, suggesting that the former positions are promising sites for introducing side chains which modulate physicochemical. properties. Preliminary inhibition studies with varying ATP concentrations suggest that, like the quinazoline-based kinase inhibitors, the pyrrolotriazine-based inhibitors bind in the ATP pocket.
- Hunt, John T.,Mitt, Toomas,Borzilleri, Robert,Gullo-Brown, Johnni,Fargnoli, Joseph,Fink, Brian,Han, Wen-Ching,Mortillo, Steven,Vite, Gregory,Wautlet, Barri,Wong, Tai,Yu, Chiang,Zheng, Xiaoping,Bhide, Rajeev
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p. 4054 - 4059
(2007/10/03)
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