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ID: ALA1144750

Journal: Bioorg Med Chem Lett

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

Authors: Gracias V, Ji Z, Akritopoulou-Zanze I, Abad-Zapatero C, Huth JR, Song D, Hajduk PJ, Johnson EF, Glaser KB, Marcotte PA, Pease L, Soni NB, Stewart KD, Davidsen SK, Michaelides MR, Djuric SW.

Abstract: 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 (IC(50)=9 and 52 nM, respectively).

CiteXplore: 18362070

DOI: 10.1016/j.bmcl.2008.03.021