Synthesis of 3-phenylnaphthalenic derivatives as new selective MT(2) melatoninergic ligands.

Article Details

Citation

Poissonnier-Durieux S, Ettaoussi M, Peres B, Boutin JA, Audinot V, Bennejean C, Delagrange P, Caignard DH, Renard P, Berthelot P, Lesieur D, Yous S

Synthesis of 3-phenylnaphthalenic derivatives as new selective MT(2) melatoninergic ligands.

Bioorg Med Chem. 2008 Sep 15;16(18):8339-48. doi: 10.1016/j.bmc.2008.08.052. Epub 2008 Aug 27.

PubMed ID
18778943 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AgomelatineMelatonin receptor type 1AKi (nM)0.06N/AN/ADetails
AgomelatineMelatonin receptor type 1BEC 50 (nM)0.1N/AN/ADetails
AgomelatineMelatonin receptor type 1BKi (nM)0.27N/AN/ADetails
MelatoninMelatonin receptor type 1AKi (nM)0.14N/AN/ADetails
MelatoninMelatonin receptor type 1BEC 50 (nM)0.49N/AN/ADetails
MelatoninMelatonin receptor type 1BKi (nM)0.41N/AN/ADetails