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 Cs2CO3, 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, pi-pi interactions, and halogen bonds could be important for efficiency. Finally, theoretical ADMET studies on pyrrolopyrazine derivatives demonstrated that pharmacokinetic phases are suitable.