Synthesis of N,N′-bis(5-arylidene-4-oxo-3,5-dihydro-4H-imidazol-2-yl)diamines bearing various linkers and biological evaluation as potential inhibitors of kinases

The synthesis in 4 steps of new N,N′-bis(5-arylidene-4-oxo-3,5-dihydro-4H-imidazol-2-yl)diamines issued from various symmetric primary diamines as linkers was reported. The key step of our strategy has been the sulphur/nitrogen displacement of (5Z)-5-arylidene-2-ethylsulfanyl-3,5-dihydro-4H-imidazol-4-ones 6 with respectively ethylenediamine 7a, piperazine 7b and N,N′-bis(3-aminopropyl)piperazine 7c using solvent-free reaction conditions under microwave irradiation with retention of configuration. These compounds were tested for their kinase inhibitory potencies toward four kinases (GSK-3α/β, DYRK1A, CLK1 and CLK3).

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A new route N,N′-bis(5-arylidene-4-oxo-3,5-dihydro-4H-imidazol-2-yl)diamines. ► N,N′-disubstituted diamines with3 points of diversity. ► Sulphur/nitrogen displacement under solvent-less microwave irradiation reaction conditions. ► Inhibitor of the CLK1 kinase.