Bioorganic and Medicinal Chemistry Letters p. 2691 - 2695 (2008)
Update date:2022-07-29
Topics:
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.
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 52 nM, respectively).
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