**5. Conclusions**

*Melatonin - The Hormone of Darkness and Its Therapeutic Potential and Perspectives*

compounds. Ramelteon, *N*-{2-[(8*S*)-1,6,7,8-tetrahydro-2H-indeno[5,4-*b*]furan-8-yl]ethyl}propanamide (**76**) [52], is a melatonin analogue approved by the FDA as a sedative-hypnotic. The following synthetic route [53], illustrated in **Figure 12**, uses dibenzoyl-*L*-tartaric acid as an acid to form the salt at the end of hydrogena-

*Examples of chiral melatoninergic analogues and side chain conformationally constrained tricyclic derivatives* 

Most of these chiral derivatives are prepared as racemates and, then, in some cases, resolved. The racemate mixture of enantiomers provides an initial estimation of the biology of these compounds, although asymmetric syntheses may then be required if one of the enantiomers exhibits a selective result. Substituents on the 3-side chain, particularly at the *β*-position, present a preference for the active conformation. This hypothesis has been investigated by assessing the melatoninergic potency of various compounds which bear in their side chain small to large substituents. An example of *α*- and *β*-methyl side chain functionalized molecules with enhanced activity is the *N*1-phenethyl-substituted indole derivatives **79** and **82** [54]. The characteristic steps of the synthesis of these probes are illustrated in **Figure 13**. Similar results, in terms of activities and related conformation, have

tion and as the resolution agent as well.

been obtained for the analogues **83**, **84**, and **85** [55–57].

**10**

**Figure 12.** *Ramelteon.*

**Figure 13.**

*83 and 84.*

A selection of key melatoninergic derivatives was reported herein. We pointed out the synthetic routes towards these melatonin analogues, first of the aromatic nucleus, then of the functionalities that have been introduced to the nucleus, and finally of those analogues with restrained conformations and those that are optically active. Much more needs to be explored about the variant functions of melatonin and through which receptor type they exert their action. The range of small molecules having agonist or antagonist effects on the melatonin receptors is large, and new scaffolds keep appearing as drug candidates in different treatments. This work is hoped to assist those seeking to explore the melatonin and melatoninergic field.
