Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands.
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.
Yous
Saíd
S
Laboratoire de Chimie Thérapeutique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, BP 83, 59006 Lille Cedex, France. syous@phare.univ-lille2.fr
Durieux-Poissonnier
Sophie
S
Lipka-Belloli
Emmanuelle
E
Guelzim
Halim
H
Bochu
Christophe
C
Audinot
Valérie
V
Boutin
Jean A
JA
Delagrange
Philippe
P
Bennejean
Caroline
C
Renard
Pierre
P
Lesieur
Daniel
D
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008550:Melatonin / Q000031:analogs & derivatives* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects*; D044094:Receptors, Melatonin; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology*
D007202:Indicators and Reagents; D008024:Ligands; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C044556:2-iodomelatonin; D008550:Melatonin