1,6-Dihydro-2H-indeno[5,4-b]furan derivatives: design, synthesis, and pharmacological characterization of a novel class of highly potent MT(2)-selective agonists.

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Koike T, Hoashi Y, Takai T, Nakayama M, Yukuhiro N, Ishikawa T, Hirai K, Uchikawa O

1,6-Dihydro-2H-indeno[5,4-b]furan derivatives: design, synthesis, and pharmacological characterization of a novel class of highly potent MT(2)-selective agonists.

J Med Chem. 2011 May 12;54(9):3436-44. doi: 10.1021/jm200221q. Epub 2011 Apr 7.

PubMed ID

21473625 [ View in PubMed

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Abstract

A novel series of 1,6-dihydro-2H-indeno[5,4-b]furan derivatives were designed and synthesized as MT(2)-selective ligands. This scaffold was identified as a potent mimic of the 5-methoxy indole core of melatonin, and introduction of a cyclohexylmethyl group at the 7-position of this scaffold afforded an MT(2)-selective ligand 15 (K(i) = 0.012 nM) with high MT(1)/MT(2) selectivity (799). Compound 15 was identified as a potent full agonist for the MT(2) subtype and exhibited reentrainment effects to a new light/dark cycle in ICR mice at 3-30 mg/kg. This result demonstrated the involvement of the MT(2) receptors in chronobiotic activity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Melatonin	Melatonin receptor type 1A	Ki (nM)	0.24	N/A	N/A	Details
Melatonin	Melatonin receptor type 1B	Ki (nM)	0.21	N/A	N/A	Details