New trisubstituted 1,2,4-triazole derivatives as potent ghrelin receptor antagonists. 3. Synthesis and pharmacological in vitro and in vivo evaluations.
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.
Moulin
Aline
A
Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Universités Montpellier 1, Montpellier 2, Montpellier Cedex 5, France.
Demange
Luc
L
Ryan
Joanne
J
Mousseaux
Delphine
D
Sanchez
Pierre
P
Bergé
Gilbert
G
Gagne
Didier
D
Perrissoud
Daniel
D
Locatelli
Vittorio
V
Torsello
Antonio
A
Galleyrand
Jean-Claude
JC
Fehrentz
Jean-Alain
JA
Martinez
Jean
J
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
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