New trisubstituted 1,2,4-triazole derivatives as potent ghrelin receptor antagonists. 3. Synthesis and pharmacological in vitro and in vivo evaluations.
Aline Moulin, Luc Demange, Joanne Ryan, Delphine Mousseaux, Pierre Sanchez, Gilbert Bergé, Didier Gagne, Daniel Perrissoud, Vittorio Locatelli, Antonio Torsello, Jean-Claude Galleyrand, Jean-Alain Fehrentz, Jean Martinez
J Med Chem | Published : 2008
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.