Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands.
Yous S,
Durieux-Poissonnier S,
Lipka-Belloli E,
Guelzim H,
Bochu C,
Audinot V,
Boutin JA,
Delagrange P,
Bennejean C,
Renard P,
Lesieur D.
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
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.
PMID: 12538005 [PubMed - indexed for MEDLINE]