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[Melatonin, a pertinent prototype for therapeutic innovation]
D Lesieur1, V Leclerc, P Chavatte
1Institut de Chimie Pharmaceutique, Université de Lille II, France.
Abstract:
Melatonin fulfils most of the requirements of a typical lead compound for rational drug design. We have rationally modified each of its structural features with a view to clarifying their role in drug-receptor interactions (affinity and activity) and to obtain agonist and antagonist ligands which could be used as pharmacological tools and/or as drugs. Molecular modelling studies allow us to propose a pharmacophore model. The naphthalenic bioisostere of melatonin (agomelatin) is currently under clinical (phase II) evaluation and two other compounds have been selected for development.
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