title: New trisubstituted 1,2,4-triazole derivatives as potent ghrelin receptor antagonists. 3. Synthesis and pharmacological in vitro and in vivo evaluations.
abstract: Ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the replacement of the alpha-aminoisobutyryl moiety by aromatic or heteroaromatic groups. Compounds 5 and 34 acted as potent in vivo antagonists of hexarelin-stimulated food intake. These two compounds did not stimulate growth hormone secretion in rodents and did not antagonize growth hormone secretion induced by hexarelin.
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Universités Montpellier 1, Montpellier 2, Montpellier Cedex 5, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Moulin
authors.forename: Luc
authors.initials: L
authors.lastname: Demange
authors.forename: Joanne
authors.initials: J
authors.lastname: Ryan
authors.forename: Delphine
authors.initials: D
authors.lastname: Mousseaux
authors.forename: Pierre
authors.initials: P
authors.lastname: Sanchez
authors.forename: Gilbert
authors.initials: G
authors.lastname: Bergé
authors.forename: Didier
authors.initials: D
authors.lastname: Gagne
authors.forename: Daniel
authors.initials: D
authors.lastname: Perrissoud
authors.forename: Vittorio
authors.initials: V
authors.lastname: Locatelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Torsello
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Galleyrand
authors.forename: Jean-Alain
authors.initials: JA
authors.lastname: Fehrentz
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D018374:LLC-PK1 Cells; D009842:Oligopeptides / Q000494:pharmacology; D010847:Picolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; C528503:N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide; C528504:N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide; D009842:Oligopeptides; D010847:Picolines; D011719:Pyrazines; D054440:Receptors, Ghrelin; D014230:Triazoles; C086184:hexarelin; D013006:Growth Hormone