The optimization of molecular geometry, study of the quantitatife structureactivity relationship (QSAR) and multilinear regression (MLR) on derivatives benzopirazine compounds have been conducted with substitution groups electron (R7) donors such as:-Br,-COOH,-NH2,-NH3,-OH and-C5H6. Molecular structure model have been done with computationally using hyperchem 8.0.10 sofware. Results geometry optimization using the semi-emperical AM1 method show the total energy of each compound by A1-A6. Determine of the relationship between descriptors included Log P, Polari, SAG, SAA, EH, EHOMO, ELUMO, ΔEG, MD and clean charge with antimalarial activity (IC50 Experiments) shows a correlation. Descriptor show a relationship with antimalarian activity (IC50 Experiments) then, determined the best QSAR equal model condocted with multilinear regression analysis using SPSS 22 program. The results of analysis obtained for the best QSAR equation model found in model 4 equation: Log 1/IC50 = 2.357-(0.041) EH + (0.297) Polari-(0.