Melatonin, structure

On the other hand, multimodality of biological activities of melatonin is well known. Therefore various derivatives are needed for carrying out its structure-activity relationship study. 1-Hydoxymelatonin (19) would be a suitable seed for developing yet unknown results. 

Figure 10.4 Chemical structures of the clinically relevant melatonin analogs, compared with melatonin (5-methoxy-N-acetyltryptamine). Agomelatine N- 2-[7-methoxy-l-naphthalenyl]ethyl)acetamide. Ramelteon ...

Dijk, D. J. Cajochen, C. (1997). Melatonin and the circadian regulation of sleep initiation, consolidation, structure, and the sleep EEG. J. Biol. Rhythms 12, 627-35. 

Melatonin probably manifests some chelating activity although its structure is very different from the structures of effective chelators (see below). 

Isotopically labeled DHPN Oa was also used as a source of [ Oa] to provide further support for the proposed structure. It was thus confirmed that Oa-mediated oxidation of melatonin yields AFMK through the intermediary of a transient endoperoxide as inferred from the fragmentation pattern of the [ 0]-labeled oxidation product. The deformyla-tion product of AFMK, namely A -acetyl-5-methoxykynuramine, was also shown to be produced. 

Several drugs with novel chemical structures have been introduced more recently for use in sleep disorders. Zolpidem, an imidazopyridine, zaleplon, a pyrazolopyrimidine, and eszopiclone, a cyclopyrrolone (Figure 22-4), although structurally unrelated to benzodiazepines, share a similar mechanism of action, as described below. Eszopiclone is the (S) enantiomer of zopiclone, a hypnotic drug that has been available outside the United States since 1989. Ramelteon, a melatonin receptor agonist, is a new hypnotic drug (see Ramelteon). Buspirone is a slow-onset anxiolytic agent whose actions are quite different from those of conventional sedative-hypnotics (see Buspirone). 

Fig. 9.5 Chemical structures of low molecular weight antioxidants Melatonin (a) ascorbic acid (Vitamin C) (b) glutathione (c) lipoic acid (d) a-tocopherol (Vitamin E) (e) and a-tocotrienol (f)...

Scientists have discovered the chemical structure of melatonin so that it can be manufactured commercially. 

Williamson, B. L. Tomlinson, A. I Mishra, P. K. Gleich, G. J. Naylor, S. 1998. Structural characterization of contaminants found in commercial preparations of melatonin similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem. Res. Toxicol., 11,234-240. 

In recent years, many physiological properties of melatonin have been described resulting in much attention in the development of synthetic compounds possessing indole ring [94]. These compounds have structural similarity to melatonin. However, the therapy of oxidative stress-related diseases has not found satisfactory application in clinical practice. This may be due to the insufficient efficacy of drugs available, their unsuitable pharmacokinetics, side effects, and toxicity. 

Figure 5.9 Molecular supergraph for a series of melatonin receptor ligands with superimposed structures of several representative training set compounds.

Modern spectroscopic methods and the structure of the hormone melatonin (Opener. Problem 14.26)... 

Indolealkylamines. GC-MS methods applied in studies of the biochemical pharmacology of indoleamines parallel work on the catecholamines. SIM assays for serotonin (5-hydroxytryptamine), 5-methoxytryptamine, JV-acetylserotonin and melatonin (5-methoxy-N-acetyltryptamine) in rat pineal and brain tissue have been described [453,469]. Pentafluoro-propionyl derivatives and structural homologue standardisation were employed with detection limits in the subpicomole range. Estimation of central indoleamine turnover in man currently depends upon metabolite determination in CSF. Ion monitoring determination of indole-3-acetic acid [454] a metabolite of tryptamine, and isotope dilution assays for 5-hydroxyindoleacetic acid (5-HIAA) [455,458] have been reported. Serotonin is converted by central monoamine oxidase to 5-HIAA and the measurement of this metabolite, formerly by fluorimetry, is of interest in patients with CNS disorders [470]. GC-MS has also contributed to the identification of N,N-dimethyltryptamine in vitro [471] and isotope dilution technique has been applied to the measurement of this metabolite in control subjects and in psychiatric patients [472]. 

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