Scaffold oriented synthesis. Part 2: design, synthesis and biological evaluation of pyrimido-diazepines as receptor tyrosine kinase inhibitors

…, Z Ji, I Akritopoulou-Zanze, C Abad-Zapatero…

文献索引：Gracias, Vijaya; Ji, Zhiqin; Akritopoulou-Zanze, Irini; Abad-Zapatero, Cele; Huth, Jeffrey R.; Song, Danying; Hajduk, Philip J.; Johnson, Eric F.; Glaser, Keith B.; Marcotte, Patrick A.; Pease, Lori; Soni, Nirupama B.; Stewart, Kent D.; Davidsen, Steven K.; Michaelides, Michael R.; Djuric, Stevan W. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 8 p. 2691 - 2695

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被引用次数: 26

摘要

We report the discovery of the pyrimido-diazepine scaffolds as novel adenine mimics. Structure-based design led to the discovery of analogs with potent inhibitory activity against receptor tyrosine kinases, such as KDR, Flt3 and c-Kit. Compound 14 exhibited low nanomolar KDR enzymatic and cellular potencies (IC50= 9 and 52nM, respectively).