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Eur J Med Chem. 2013 Jan;59:283-95. doi: 10.1016/j.ejmech.2012.11.030. Epub 2012 Nov 24.

Synthesis and biological evaluation of N-aryl-7-methoxybenzo[b]furo[3,2-d]pyrimidin-4-amines and their N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amine analogues as dual inhibitors of CLK1 and DYRK1A kinases.

Author information

1
Université de Rouen, Laboratoire de Chimie Organique et Bio-organique, Réactivité et Analyse (C.O.B.R.A.), CNRS UMR 6014 & FR3038, Institut de Recherche en Chimie Organique Fine (I.R.C.O.F.) rue Tesnière, 76130 Mont Saint-Aignan, France.

Abstract

Novel N-aryl-7-methoxybenzo[b]furo[3,2-d]pyrimidin-4-amines (1) and their N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amine analogues (2) were designed and prepared for the first time via microwave-accelerated multi-step synthesis. Various anilines were condensed with N'-(2-cyanaryl)-N,N-dimethylformimidamide intermediates obtained by reaction of 3-amino-6-methoxybenzofuran-2-carbonitrile (3) and 3-amino-6-methoxybenzothiophene-2-carbonitrile (4) precursors with dimethylformamide dimethylacetal. The inhibitory potency of the final products against five protein kinases (CDK5/p25, CK1δ/ε, GSK3α/β, DYRK1A and CLK1) was estimated. Compounds (2a-z) turned out to be particularly promising for the development of new pharmacological dual inhibitors of CLK1 and DYRK1A kinases.

PMID:
23237976
DOI:
10.1016/j.ejmech.2012.11.030
[Indexed for MEDLINE]

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