• Rüdiger Faust, Peter J Garratt, Maria Angeles Trujillo Pérez, Vincent J-D Piccio, Christian Madsen, Ane Stenstrøm, Bente Frølund, Kathryn Davidson, Muy-Teck Teh, and David Sugden.
• Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
• Bioorg. Med. Chem. 2007 Jul 1;15(13):4543-51.

AbstractA series of 7-substituted melatonin and 1-methylmelatonin analogues were prepared and tested against human and amphibian melatonin receptors. 7-Substituents reduced the agonist potency of all the analogues in the Xenopus laevis melanophore assay, 7-bromomelatonin (5d) and N-butanoyl 7-bromo-5-methoxytryptamine (5f) being the most active compounds, but both were 42-fold less potent than melatonin (1). Whereas all the analogues bind with lower affinity at the human MT(1) receptor than melatonin, 5d, 5f and N-propanoyl 7-bromo-5-methoxytryptamine (5e) show a similar binding affinity to melatonin at the MT(2) receptor and consequently show some MT(2) selectivity. These results suggest that the receptor pocket around C-7 favours binding by an electronegative group, suggesting an electropositive region in this area of the receptor.

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