Novel 3-arylethynyl-substituted thieno[3,4-b]pyrazine derivatives as human transglutaminase 2 inhibitors.

In the process of optimization, we developed a novel core skeleton of thieno[3,4-b]pyrazine via GK-13. The derivatives synthesized were shown to inhibit TGase 2 activity in cancer cells. Some of the hit compounds such as the arylethynyl group-coupled thieno[3,4-b]pyrazine derivatives were shown to exhibit promising activity for use as potential therapeutic small-molecules in renal cancer by inhibiting TGase 2 activity.