Design and synthesis of 1-(2-alkanamidoethyl)-6-methoxy-7-azaindole derivatives as potent melatonin agonists

Matthieu Jeanty; Franck Suzenet; Philippe Delagrange; Olivier Nosjean; Jean A Boutin; Daniel H Caignard; Gérald Guillaumet

doi:10.1016/j.bmcl.2011.02.097

Design and synthesis of 1-(2-alkanamidoethyl)-6-methoxy-7-azaindole derivatives as potent melatonin agonists

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2316-9. doi: 10.1016/j.bmcl.2011.02.097. Epub 2011 Feb 26.

Authors

Matthieu Jeanty¹, Franck Suzenet, Philippe Delagrange, Olivier Nosjean, Jean A Boutin, Daniel H Caignard, Gérald Guillaumet

Affiliation

¹ Institut de Chimie Organique et Analytique, Université d'Orléans, UMR-CNRS 6005, BP 6759, rue de Chartres, 45067 Orléans Cedex 2, France.

PMID: 21420861
DOI: 10.1016/j.bmcl.2011.02.097

Abstract

A series of 7-azaindolic ligands bearing a methoxy group and a N-acetyl chain as melatoninergic pharmacophores were synthesized and their binding affinities towards MT(1) and MT(2) receptors were evaluated. Compounds 7a-c and 12 (cyclohexyl ring connected at C-2 and C-3 position) appears as important melatonin MT(2) and MT(1) receptors agonists. On the other hand, the presence of basic groups (amines) at position C-3 was detrimental to the melatoninergic affinities.

MeSH terms

Drug Design
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / pharmacology
Protein Binding
Receptor, Melatonin, MT1 / agonists*
Receptor, Melatonin, MT1 / metabolism
Receptor, Melatonin, MT2 / agonists*
Receptor, Melatonin, MT2 / metabolism

Substances

7-azaindole dimer
Indoles
Receptor, Melatonin, MT1
Receptor, Melatonin, MT2