5-Halobenzothiophene Analogues of Melatonin: Synthesis and Affinity for mt1 and MT2 Receptors in Man

A novel series of melatonin analogues based on the benzothiophene nucleus is described. In these compounds the methoxy group was replaced by electron-attracting groups such halogens (Br and Cl) with the aim of supplementing structure-affinity relationships on melatoninergic ligands. Target derivatives were prepared from the corresponding 4-halo-thiophenol. Some of these derivatives had high affinity for mt1 and MT2 receptors, almost as high as that of melatonin. These results prove that the methoxy group is not an essential requirement for binding to melatoninergic receptors.