RECENT DEVELOPMENTS IN MELATONIN RECEPTOR LIGANDS

In recent years, many physiological properties of melatonin have been described resulting in much interest in the development of synthetic c ompounds possessing agonist or antagonist properties for melatonin rec eptors. These compounds have structural similarity to melatonin, being derivatives of either substituted tryptamines or of bioisosteric moie ties 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 c ompounds. The important roles of substitutions on the 2 position of th e indole ring and of the alkyl chain of the acyl group have been highl ighted. 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 be en claimed to be useful for the treatment of depression, sleep disorde rs and disturbances of circadian rhythm. Some patents have claimed als o anti-ovulatory or antiproliferative properties. No compounds develop ed so far discriminate between the different melatonin receptor subtyp es and few compounds have been described as antagonists for melatonin receptors.