Synthesis of new N-(arylcyclopropyl)acetamides and N-(arylvinyl)acetamides as conformationally-restricted ligands for melatonin receptors.

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Morellato L, Lefas-Le Gall M, Langlois M, Caignard DH, Renard P, Delagrange P, Mathe-Allainmat M

Synthesis of new N-(arylcyclopropyl)acetamides and N-(arylvinyl)acetamides as conformationally-restricted ligands for melatonin receptors.

Bioorg Med Chem Lett. 2013 Jan 15;23(2):430-4. doi: 10.1016/j.bmcl.2012.11.069. Epub 2012 Nov 29.

PubMed ID

23265885 [ View in PubMed

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Abstract

N-(Arylcyclopropyl)acetamides and N-(arylvinyl)acetamides or methyl ureas have been prepared as constrained analogues of melatonin. The affinity of these new compounds for chicken brain melatonin receptors and recombinant human MT(1) and MT(2) receptors was evaluated using 2-[(125)I]-iodomelatonin as radioligand. Strict ethylenic or cyclopropyl analogues of the commercialized agonist agomelatine (Valdoxan(R)) were equipotent to agomelatine in binding bioassays. However, the ethylenic analogue was more effective than the cyclopropyl one in the melanophore aggregation bioassay, but was still less potent than the disubstituted 2,7-dimethoxy-naphtalenic compounds.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Agomelatine	Melatonin receptor type 1A	Ki (nM)	0.1	N/A	N/A	Details
Agomelatine	Melatonin receptor type 1B	Ki (nM)	0.1	N/A	N/A	Details
Melatonin	Melatonin receptor type 1A	Ki (nM)	0.2	N/A	N/A	Details
Melatonin	Melatonin receptor type 1B	Ki (nM)	0.5	N/A	N/A	Details