Melatonin, a suitable lead compound for rational drug design

Melatonin fulfils most of the requirements of a typical lead compound for r ational drug design. We have rationally modified each of its structural fea tures with a view to clarifying their role in drug-receptor interactions (a ffinity and activity) and to obtain agonist and antagonist ligands which co uld be used as pharmacological tools and/or as drugs. Molecular modelling s tudies allow us to propose a pharmacophore model. The naphthalenic bioisost ere of melatonin (agomelatin) is currently under clinical (phase II) evalua tion and two other compounds have been selected for development.