Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands

• Published in: Bioorganic & medicinal chemistry 2003-03, Vol.11 (5), p.753-759
• Main Authors: YOUS, Saïd, DURIEUX-POISSONNIER, Sophie, LESIEUR, Daniel, LIPKA-BELLOLI, Emmanuelle, GUELZIM, Halim, BOCHU, Christophe, AUDINOT, Valérie, BOUTIN, Jean A, DELAGRANGE, Philippe, BENNEJEAN, Caroline, RENARD, Pierre
• Format: Article
• Language: English
• Subjects: Animals; Binding, Competitive - drug effects; Biological and medical sciences; CHO Cells; Cricetinae; Dose-Response Relationship, Drug; Drug Design; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Guinea Pigs; Humans; Indicators and Reagents; Ligands; Magnetic Resonance Spectroscopy; Medical sciences; Melatonin - analogs & derivatives; Melatonin - metabolism; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptors, Cell Surface - drug effects; Receptors, Cytoplasmic and Nuclear - drug effects; Receptors, Melatonin; Structure-Activity Relationship; Tetrahydronaphthalenes - chemical synthesis; Tetrahydronaphthalenes - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(02)00473-X

Tetrahydronaphthalenic analogues of melatonin have been synthesized and evaluated as melatonin receptor ligands. Introduction of a phenyl substituent in the 3-position of the tetraline ring allows to obtain MT(2) selective ligands. Activity and MT(2) selectivity can be modulated with suitable modifications of the N-acyl substituent. The (+)-(RR)-cis enantiomer of the N-[2-(7-methoxy-3-phenyl-1,2,3,4-tetrahydro-naphthalen-1-yl)ethyl]cyclobutyl carboxamide (14) is one of the most MT(2) selective ligands described until now and behaves as an antagonist.