Design and synthesis of naphthalenic dimers as selective MT1 melatoninergic ligands.
We report the synthesis and binding properties at MT(1) and MT(2) receptors of the first example of agomelatine (N-[2-(7-methoxynaphth-1-yl)ethyl]acetamide) dimers in which two agomelatine moieties are linked together through their methoxy substituent by a polymethylene side chain according to the "bivalent ligand" approach. Some of these compounds behave as MT(1)-selective ligands. The most selective one (5) behaves as an antagonist.
Descamps-François
Carole
C
Faculté de Pharmacie, Laboratoire de Chimie Thérapeutique, Université de Lille 2, 3 Rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France.
Yous
Saïd
S
Chavatte
Philippe
P
Audinot
Valérie
V
Bonnaud
Anne
A
Boutin
Jean A
JA
Delagrange
Philippe
P
Bennejean
Caroline
C
Renard
Pierre
P
Lesieur
Daniel
D
D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D019281:Dimerization; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000378:metabolism*; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D044094:Receptors, Melatonin; D013329:Structure-Activity Relationship
D000081:Acetamides; D008024:Ligands; D009281:Naphthalenes; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; C084711:agomelatine; D008550:Melatonin