2. Academic Validation
  3. New trisubstituted 1,2,4-triazoles as ghrelin receptor antagonists

New trisubstituted 1,2,4-triazoles as ghrelin receptor antagonists

  • Bioorg Med Chem Lett. 2015 Jan 1;25(1):20-4. doi: 10.1016/j.bmcl.2014.11.031.
Anne-Laure Blayo 1,  Mathieu Maingot 1,  Babette Aicher 2,  Céline M'Kadmi 1,  Peter Schmidt 2,  Gilbert Müller 2,  Michael Teifel 2,  Eckhard Günther 2,  Didier Gagne 1,  Séverine Denoyelle 1,  Jean Martinez 1,  Jean-Alain Fehrentz 3
Affiliations

Affiliations

  • 1 Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier I et Université Montpellier II, BP 14491, Faculté de Pharmacie, bât. E, 3(ème) étage, 15 avenue Charles Flahault, 34093 Montpellier Cedex 5, France.
  • 2 Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt am Main, Germany.
  • 3 Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier I et Université Montpellier II, BP 14491, Faculté de Pharmacie, bât. E, 3(ème) étage, 15 avenue Charles Flahault, 34093 Montpellier Cedex 5, France. Electronic address: jean-alain.fehrentz@univ-montp1.fr.
PMID: 25435152 DOI: 10.1016/j.bmcl.2014.11.031
Abstract

Ghrelin receptor ligands based on a trisubstituted 1,2,4-triazole scaffold were recently synthesized and evaluated for their in vitro affinity for the GHS-R1a receptor and their biological activity. In this study, replacement of the α-aminoisobutyryl (Aib) moiety (a common feature present in numerous growth hormone secretagogues described in the literature) by aromatic and heteroaromatic groups was explored. We found potent antagonists incorporating the picolinic moiety in place of the Aib moiety. In an attempt to increase affinity and activity of our lead compound 2, we explored the modulation of the pyridine ring. Herein we report the design and the structure-activity relationships study of these new ghrelin receptor ligands.

Keywords

1,2,4-Triazole scaffold; Antagonists; GHS-R1a, ghrelin receptor; SAR study; Structural modulation.

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