chapter  L3
7 Pages

From Lead Compound to Dianilino-Phthalimides

WithGraham Patrick

Every medicinal chemistry project requires a lead compound – a compound that either shows some useful biological activity or has some affinity for the target receptor or enzyme under study. Simplification is a tactic that is often tried on complex lead compounds with the aim of finding a simpler structure that is easier to synthesize and retains the important structural features associated with activity. The dianilino-phthalimides were hydroxylated by metabolic enzymes at the para position of the aniline ring. The propeller-shaped conformation of the dianilino-phthalimides is formed in order to relieve a steric clash between protons which would occur if the structure was planar. In order to prevent drug metabolism, fluorine substituents were placed at the para positions to act as metabolic blockers. A variety of drug design strategies were carried out on the dianilino-phthalimides to see whether activity could be improved.