Design, synthesis and pharmacological evaluation of novel naphthalenic derivatives as selective MT(1) melatoninergic ligands.
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Mesangeau C, Peres B, Descamps-Francois C, Chavatte P, Audinot V, Coumailleau S, Boutin JA, Delagrange P, Bennejean C, Renard P, Caignard DH, Berthelot P, Yous S
Design, synthesis and pharmacological evaluation of novel naphthalenic derivatives as selective MT(1) melatoninergic ligands.
Bioorg Med Chem. 2010 May 15;18(10):3426-36. doi: 10.1016/j.bmc.2010.04.008. Epub 2010 Apr 7.
- PubMed ID
- 20444610 [ View in PubMed]
- Abstract
Novel heterodimer analogues of melatonin were synthesized, when agomelatine (1) and various aryl units are linked via a linear alkyl chain through the methoxy group. The compounds were tested for their actions at melatonin receptors. Several of these ligands are MT(1)-selective with nanomolar or subnanomolar affinity. In addition, while most of the derivatives behave as partial agonists on one or both receptor subtypes, N-[2-(7-{4-[6-(1-methoxycarbonylethyl)naphthalen-2-yloxy]butoxy}naphthalen-1-yl)e thyl]acetamide (36), a subnanomolar MT(1) ligand with an 11-fold preference over MT(2) receptors, is a full antagonist on both receptors. Our results also confirm that the selectivity seen for the MT(1) receptor arises predominantly from steric factors and is not a consequence of the bridging of melatonin receptor dimers.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Agomelatine Melatonin receptor type 1A EC 50 (nM) 1.6 N/A N/A Details Agomelatine Melatonin receptor type 1B EC 50 (nM) 0.1 N/A N/A Details Melatonin Melatonin receptor type 1A EC 50 (nM) 2.2 N/A N/A Details Melatonin Melatonin receptor type 1B EC 50 (nM) 0.49 N/A N/A Details