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Issue 9, 2014
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Synthesis, chiral resolution, absolute configuration assignment and pharmacological evaluation of a series of melatoninergic ligands

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Abstract

We report herein the racemic resolution and pharmacological evaluation of naphthalenic ligand analogues of compound 3a. Propionamide 3b and fluoroacetamide 3c showed a good pharmacological profile towards MT1, MT2 and 5-HT2C. Hence, their enantiomers were successfully separated from racemates (±)-3a and (±)-3b and evaluated for their binding affinities and antidepressant activity. Binding results revealed that (−)-R-enantiomers were more potent than (+)-S-enantiomers. Furthermore, the (−)-R-enantiomers exhibited high binding affinities with partial agonist activity at melatonin MT1 and MT2 receptor subtypes and antagonist activity at the serotonin 5-HT2C receptor subtype. The R-fluoroacetamide 3c demonstrated the most potent binding affinity towards the 5-HT2C receptor subtype (pKi = 6.73 ± 0.02).

Graphical abstract: Synthesis, chiral resolution, absolute configuration assignment and pharmacological evaluation of a series of melatoninergic ligands

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Publication details

The article was received on 31 Mar 2014, accepted on 19 May 2014 and first published on 28 May 2014


Article type: Concise Article
DOI: 10.1039/C4MD00149D
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Citation: Med. Chem. Commun., 2014,5, 1303-1308

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    Synthesis, chiral resolution, absolute configuration assignment and pharmacological evaluation of a series of melatoninergic ligands

    M. Ettaoussi, B. Pérès, C. Jarry, O. Nosjean, J. A. Boutin, A. Gohier, C. Mannoury la Cour, D. Caignard, P. Delagrange, P. Berthelot and S. Yous, Med. Chem. Commun., 2014, 5, 1303
    DOI: 10.1039/C4MD00149D

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