Practical approach to N -benzyl derivatives of 2-amino-8-methoxy-4 H-chromene-3-carbonitrile by reductive amination: Exploration of their effects against protein kinases and in silico ADME profiling

The synthesis of 2-benzylamino-8-methoxy-4 H -chromene-3-carbonitriles 7(a-e) has been realized in four steps, via reductive amination from the 2-amino-8-methoxy-4 H -chromene-3-carbonitrile 4 as key intermediate platform with para- and meta- substituted benzaldehydes 5(a-e) , in good overall yields. The physicochemical properties of 7(a-e) and also their aldimines 6(a-e) precursors have been determined using the Swiss ADME server platform according to the Lipinski's descriptors. Biological assays with a panel of six protein kinases such as Hs CDK5-p25, Hs CDK9/cyclin T, Hs Pim1, Hs Haspin, Ssc GSK-3a/ beta and Ssc CK1 delta/ epsilon showed that aldimines 6(a,b) and 6e are potentially interesting because they showed good percentage of residual activities against Hs Pim1 and Hs Haspin.

Automated summary

The synthesis of 2-benzylamino-8-methoxy-4H-chromene-3-carbonitriles 7(a-e) was achieved through a four-step process, using reductive amination of 2-amino-8-methoxy-4H-chromene-3-carbonitrile 4 with para- and meta-substituted benzaldehydes 5(a-e). The resulting compounds 7(a-e) and their aldimines 6(a-e) were characterized using the Swiss ADME server platform and showed potential activity against Hs Pim1 and Hs Haspin protein kinases.