Recent developments in melatonin receptor ligands

Abstract

In recent years, many physiological properties of melatonin have been described resulting in much interest in the development of synthetic compounds possessing agonist or antagonist properties for melatonin receptors. These compounds have structural similarity to melatonin, being derivatives of either substituted tryptamines or of bioisosteric moieties of the indole ring such as benzothiophene, indene and naphthalene. Research to determine the structural parameters of the melatonergic pharmacophore led to the synthesis of potent constrained, polycyclic compounds. The important roles of substitutions on the 2 position of the indole ring and of the alkyl chain of the acyl group have been highlighted. The ethylamido chain seems to prefer the flexible conformation and a folded conformer has been shown to be the active conformation. Almost all of the compounds described have been patented. They have been claimed to be useful for the treatment of depression, sleep disorders and disturbances of circadian rhythm. Some patents have claimed also anti-ovulatory or antiproliferative properties. No compounds developed so far discriminate between the different melatonin receptor subtypes and few compounds have been described as antagonists for melatonin receptors.

• circadian rhythm
• melatonergic agent
• melatonin
• melatonin receptors
• sleep disorders