Synthesis of New Melatoninergic Ligands Including Azaindole Moiety

Abstract

A novel series of melatonin analogues, based on the azaindole nucleus is described.These compounds are prepared in several steps directly from the commercial available 7-azaindole or from substituted amino-, iodo-orland nitropyridines using a catalysed palladium reaction or vicarious nucleophilic substitution of hydrogen (VNS) in order to elaborate the 6-, 5-and 4-azaindole derivatives respectively.Melatonin (Figure 1) is a pineal hormone which regulates a variety of endocrinological, neurophysiological, and behavioural functions in vertebrates.It is now recognised to be the regulator of circadian rhythm in humans and of seasonal breeding in different animal species.' Figure I MelatoninMelatonin also appears to be involved in a number of physiological and pathological conditions, and there is strong evidence for its use in pathologies associated with circadian rhythm disorders.It was shown that administration of melatonin in humans could altercate jet lag,2 induce sleep: and advance the sleep phase of subjects with delayed sleep phase syndrome.4Numerous studies on elderly people or depressed patients have also reported a decrease in overnight melatonin biosynthesis, thus suggesting a