Design and structure activity relationships of naphthalenic ligands of the melatonin receptors

Publisher Summary This chapter presents design and structure activity relationships of naphthalenic ligands of the melatonin receptors. Melatonin is secreted primarily by the pineal gland. This secretion exhibits a photoperiodic rhythm, in which the highest levels are seen during the dark period. The physiological role of melatonin is best known in photoperiodic animals for which it has been shown to regulate and synchronize biological rhythms such as metabolism, hibernation, reproduction, body weight and temperature, pelage color, and growth. Melatonin has a relatively simple structure which is appropriate to chemical modifications. The indole heterocycle is the main target of the metabolic inactivation. It is replaced with various bioisosteric rings. The most potent of these bioisosteres is selected as a new lead for pharmacomodulation, in view to clarify the role of the pharmacophores and the structure activity relationships. Affinity is evaluated by a radioligand binding assay using and 2 iodo( 125 I) melatonin and sheep pars tuberalis membranes.