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Synthesis of novel 7-substituted pyrido[2′,3′:4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues and evaluation of their inhibitory activity against Ser/Thr kinases.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Dec2013, Vol. 23 Issue 24, p6784-6788. 5p. - Publication Year :
- 2013
-
Abstract
- Abstract: The efficient synthesis of 7-substituted pyrido[2′,3′: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 49nM and proved to be specific to CLK1 among the panel of tested kinases. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 23
- Issue :
- 24
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 92641326
- Full Text :
- https://doi.org/10.1016/j.bmcl.2013.10.019