Mortality and morbidity caused by viruses are a global health problems. Therefore, there is always a need to create novel therapeutic agents and refine existing ones to maximize their efficacy. Our lab has produced benzoquinazolines derivatives that have proven effective activity as antiviral compounds against herpes simplex (HSV 1 and 2), coxsackievirus B4 (CVB4), and hepatitis viruses (HAV and HCV). This in vitro study was aimed at investigating the effectiveness of benzoquinazoline derivatives1–16against adenovirus type 7 and bacteriophage phiX174 using a plaque assay. The cytotoxicity against adenovirus type 7 was also performed in vitro, using a MTT assay. Most of the compounds exhibited antiviral activity against bacteriophage phiX174. However, compounds1,3,9, and11showed statistically significant reductions of 60–70% against bacteriophage phiX174. By contrast, compounds3,5,7,12,13, and15were ineffective against adenovirus type 7, and compounds6and16had remarkable efficacy (50%). Using the MOE-Site Finder Module, a docking study was carried out in order to create a prediction regarding the orientation of the lead compounds (1,9, and11). This was performed in order to investigate the activity of the lead compounds1,9, and11against the bacteriophage phiX174 by locating the ligand–target protein binding interaction active sites.