Synthesis of 3-phenylnaphthalenic derivatives as new selective MT(2) melatoninergic ligands.
A series of naphthalenic analogues of melatonin were prepared and evaluated as melatonin receptor MT(2) selective ligands. Activity and MT(2) selectivity can be modulated with suitable variations of the C-3 phenyl and the acyl group on the C-1 side chain. Surprisingly, in contrast with what had been previously described in other series (2-benzylindoles, 2-benzylbenzofurans and 3-phenyltetralins), the presence of a C-3 phenyl with a functional group on the meta position seems to be primordial for MT(2) affinity and selectivity. Indeed, N-[2-(3-(3-hydroxymethylphenyl)-7-methoxynaphth-1-yl)ethyl]acetamide (21) is one of the best MT(2) selective ligands described until now and behaves as an antagonist.
Poissonnier-Durieux
Sophie
S
Faculté de Pharmacie, Laboratoire de Chimie Thérapeutique (EA 1043), 3 rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France.
Ettaoussi
Mohamed
M
Pérès
Basile
B
Boutin
Jean A
JA
Audinot
Valérie
V
Bennejean
Caroline
C
Delagrange
Philippe
P
Caignard
Daniel Henri
DH
Renard
Pierre
P
Berthelot
Pascal
P
Lesieur
Daniel
D
Yous
Saïd
S
D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D005663:Furans / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry; D008024:Ligands; D008550:Melatonin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology*; D011869:Radioligand Assay; D044123:Receptor, Melatonin, MT2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000081:Acetamides; D005663:Furans; D007211:Indoles; D008024:Ligands; D009281:Naphthalenes; D044123:Receptor, Melatonin, MT2; D008550:Melatonin