title: 7-Substituted-melatonin and 7-substituted-1-methylmelatonin analogues: effect of substituents on potency and binding affinity.
abstract: A 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.
authors: Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
authors: Rüdiger
authors: R
authors: Faust
authors: Peter J
authors: PJ
authors: Garratt
authors: Maria Angeles
authors: MA
authors: Trujillo Pérez
authors: Vincent J-D
authors: VJ
authors: Piccio
authors: Christian
authors: C
authors: Madsen
authors: Ane
authors: A
authors: Stenstrøm
authors: Bente
authors: B
authors: Frølund
authors: Kathryn
authors: K
authors: Davidson
authors: Muy-Teck
authors: MT
authors: Teh
authors: David
authors: D
authors: Sugden
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D008550:Melatonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D000975:Antioxidants; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D011994:Recombinant Proteins; D008550:Melatonin