Design and synthesis of 3-phenyltetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands. Part II.
Following our studies of the melatoninergic receptors, we have developed new tetrahydronaphthalenic derivatives of melatonin that have been tested as selective melatonin receptors ligands. Regarding the role of the phenyl substituent to obtain selective ligands, modulation of selectivity and activity have been achieved by modifications of the acyl group and substitutions on the phenyl ring. Ten of the seventeen evaluated derivatives have MT(2) receptor affinity similar to that of melatonin. Moreover, we have achieved remarkable MT(2) selectivity over MT(1) (selectivity >100) and have been able to further extend the RSA of the tetrahydrophthalenic series. However, the compounds presented here display partial agonist or antagonist behavior instead of full agonist.
Durieux
Sophie
S
Laboratoire de Chimie Thérapeutique (EA 1043), Université Lille Nord de France, Faculté des Sciences Pharmaceutiques et Biologiques, BP 83, 59006 Lille Cedex, France.
Chanu
Angéline
A
Bochu
Christophe
C
Audinot
Valérie
V
Coumailleau
Sophie
S
Boutin
Jean A
JA
Delagrange
Philippe
P
Caignard
Daniel H
DH
Bennejean
Caroline
C
Renard
Pierre
P
Lesieur
Daniel
D
Berthelot
Pascal
P
Yous
Saïd
S