A molecular approach to the study of structure-activity correlation for some amphetamines

Drug activity depends on both the fine as well as the gross structure of the molecule. In this work, the properties of the molecule that are dependent on its fine structure such as: dipole moment, ionization potential and energies of the HOMO and LUMO were calculated for the optimized geometry of some drugs using Ab initio method and the GAMESS program. At physiological pH, the amine part of the drug would be partially protonated, the calculations were carried out on both the charged and the free base forms. Attempts to correlate the calculated parameters to the hallucinogenic activity of the studied drugs showed that a number of correlations could be obtained. Mathematical relations between the activity and the structural parameters were derived for the studied drugs. It should be noted that the gross properties of the molecule (size, geometry and lipophilicity) are important factors in determining the drug activity.