Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease and epilepsy are among the most serious health problems. The molecular pathogenesis of neurodegenerative disorders is associated with mitochondrial dysfunction, oxidative stress, and apoptosis. In this study, first we aim to synthesize to imidazo[2,1-c][1,2,4]triazines derivatives and then to evaluate their protective and anti-apoptotic effects in cellular models of oxidative stress in human neuroblastoma cell line (SH-SY5Y cells). Protein analyses were made to assess the potential neuroprotective effects of the synthesized compounds against H2O2-induced toxicity. Our results provide that both activation of PI3K/Akt cascade and inhibition of ERK signaling are involved in neuroprotection by four compounds and further investigations are needed to reveal their potential in specific disease models.