Efficient synthesis of novel disubstituted pyrido[3,4-b]pyrazines for the design of protein kinase inhibitors

A novel family of disubstituted pyrido [3,4-b] pyrazine-based compounds was discovered as valuable series for the design of promising protein kinase inhibitors. SAR study allowed the identification of 4-(piperidin-1-yl) aniline moiety as pharmacophoric group, in C-5 or C-8 positions of the pyrido [3,4-b] pyrazine ring, for binding to the selected therapeutic targets. Several analogues were active at low micromomolar IC50 values against a panel of seven cancer-related protein kinases providing an excellent starting point for further drug discovery optimization.