Heterocyclic compounds represent an important class of biologically active molecules; specifically those containing the substituted imide nucleus have been shown to possess high biological activities. Phthalimide derivatives have been found to exhibit industrial, agricultural and biological applications. A series of phthalimide derivatives were synthesized and studied for their acute oral toxicity as per the OECD guidelines and anxiolytic activity using Elevated plus-maze animal model. The compounds were screened for anxiolytic activity using diazepam as the standard. Anxiolytic activity was calculated based on the per cent open arm entries and average time spent by mice on open arms. The QSAR studies were carried out by using molecular modeling software Maestro from Schrodinger, USA. The best QSAR model was obtained when anxiolytic activity was correlated with ionization potential (IP) values of phthalimide derivatives.