Synthesis of novel 1,3-disubstituted pyrrolo[1,2-a]pyrazine derivatives and antiproliferative effects on glioblastoma cell line

Novel pyrrolopyrazine derivatives were synthesized according to a very simple protocol starting from N- propargylated-2-acyl-pyrroles. These derivatives were obtained in good to excellent yields (68–94%) in the presence of ammonium acetate and Cs 2 CO 3 , and then subjected to cytotoxicity testing against glioblastoma cell line T98G. Among the tested molecules, those that cause 68.9%, 59.1%, and 37.5% cell death, were identified as lead compounds. The structure–activity relationship (SAR) study revealed that conformation, π–π interactions, and halogen bonds could be important for efficiency. Finally, theoretical ADMET studies on pyrrolopyrazine derivatives demonstrated that pharmacokinetic phases are suitable. Graphic abstract