Melatonin, a pertinent prototype for therapeutic innovation
Lesieur, D.; Leclerc, V.; Chavatte, P.; Marot, C.; Renard, P.; Guardiola-Lemaitre, B.
Therapie 53(5): 429-437
1998
ISSN/ISBN: 0040-5957 PMID: 9921034 Document Number: 494618
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.