Preparation and pharmacological evaluation of a novel series of 2-(phenylthio)benzo[b]thiophenes as selective MT2 receptor ligands.

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Mesangeau C, Fraise M, Delagrange P, Caignard DH, Boutin JA, Berthelot P, Yous S

Preparation and pharmacological evaluation of a novel series of 2-(phenylthio)benzo[b]thiophenes as selective MT2 receptor ligands.

Eur J Med Chem. 2011 May;46(5):1835-40. doi: 10.1016/j.ejmech.2011.02.044. Epub 2011 Feb 23.

PubMed ID

21392858 [ View in PubMed

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Abstract

A series of N-(2-(5-fluoro-2-(4-fluorophenylthio)benzo[b]thiophen-3-yl)ethyl)acylamides was synthesized and evaluated for binding affinity and intrinsic activity at melatonin receptors. The affinity of each compound for the melatonin receptors was determined by binding studies on cloned human MT1 and MT2 receptors expressed in CHO cells. Agonist and antagonist potency was measured on the [35S]GTPgammaS binding assay for the most interesting compounds. The new derivatives 8-14 showed modest to high selectivity (between 4 and 220) for MT2 receptors. The most selective compound, N-(2-(5-fluoro-2-(4-fluorophenylthio)benzo[b]thiophen-3-yl)ethyl)but-3-enamide (14), an MT2 ligand with affinity for the MT2 receptor similar to that of melatonin and a 220-fold preference over MT1 receptors, acts as a partial agonist. In addition, N-(2-(5-fluoro-2-(4-fluorophenylthio)benzo[b]thiophen-3-yl)ethyl)propionamide (9), a nanomolar MT2 ligand with a good selectivity ratio (MT1/MT2=51) shows antagonist activity on both melatonin receptors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Melatonin	Melatonin receptor type 1A	Ki (nM)	0.22	N/A	N/A	Details
Melatonin	Melatonin receptor type 1B	Ki (nM)	0.35	N/A	N/A	Details