Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593336 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
The efficient synthesis of 7-substituted pyrido[2â²,3â²:4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues is described. 3,5-Dibromopyridine was converted into 3-amino-6-bromofuro[3,2-b]pyridine-2-carbonitrile intermediate which was formylated with DMFDMA. Functionalization at position 7 of the tricyclic scaffold was accomplished, before or after cyclisation step, by palladium-catalyzed Suzuki-Miyaura cross-coupling while the pyrimidin-4-amines and N-aryl counterparts were synthesized by microwave-assisted formamide degradation and Dimroth rearrangement, respectively. The final products were evaluated for their potent inhibition of a series of five Ser/Thr kinases (CDK5/p25, CK1δ/ε, CLK1, DYRK1A, GSK3α/β). Compound 35 showed the best inhibitory activity with an IC50 value of 49 nM and proved to be specific to CLK1 among the panel of tested kinases.
Related Topics
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Authors
Emmanuel Deau, Yvonnick Loidreau, Pascal Marchand, Marie-Renée Nourrisson, Nadège Loaëc, Laurent Meijer, Vincent Levacher, Thierry Besson,