title: New trisubstituted 1,2,4-triazoles as ghrelin receptor antagonists.
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.
authors.affiliation: 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.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Blayo
authors.affiliation: 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.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Maingot
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt am Main, Germany.
authors.forename: Babette
authors.initials: B
authors.lastname: Aicher
authors.affiliation: 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.
authors.forename: Céline
authors.initials: C
authors.lastname: M'Kadmi
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schmidt
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt am Main, Germany.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Müller
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt am Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Teifel
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt am Main, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Günther
authors.affiliation: 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.
authors.forename: Didier
authors.initials: D
authors.lastname: Gagne
authors.affiliation: 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.
authors.forename: Séverine
authors.initials: S
authors.lastname: Denoyelle
authors.affiliation: 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.
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.affiliation: 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.
authors.forename: Jean-Alain
authors.initials: JA
authors.lastname: Fehrentz
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D054440:Receptors, Ghrelin; D014230:Triazoles; C045575:1,2,4-triazole
keywords: 1,2,4-Triazole scaffold; Antagonists; GHS-R1a, ghrelin receptor; SAR study; Structural modulation