Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1

Luc Demange, Damien Boeglin, Aline Moulin, Delphine Mousseaux, Joanne Ryan, Gilbert Bergé, Didier Gagne, Annie Heitz, Daniel Perrissoud, Vittorio Locatelli, Antonio Torsello, Jean Claude Galleyrand, Jean Alain Fehrentz, Jean Martinez

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90 Citations (Scopus)


A new series of growth hormone secretagogue (GHS) analogues based on the 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and their ability to stimulate intracellular calcium release to the cloned hGHS-1a ghrelin receptor expressed in LLC PK-1 cells. We have synthesized potent ligands of this receptor, some of them behaving as agonists, partial agonists, or antagonists. Some compounds among the most potent, i.e., agonist 29c (JMV2873), partial agonists including 21b (JMV2810), antagonists 19b (JMV2866) and 19c (JMV2844), were evaluated for their in vivo activity on food intake, after sc injection in rodents. Some compounds were found to stimulate food intake like hexarelin; some others were identified as potent hexarelin antagonists in this assay. Among the tested compounds, 21b was identified as an in vitro ghrelin receptor partial agonist, as well as a potent in vivo antagonist of hexarelin-stimulated food intake in rodents. Compound 21b was without effect on GH release from rat. However, in this series of compounds, it was not possible to find a clear correlation between in vitro and in vivo results.

Original languageEnglish
Pages (from-to)1939-1957
Number of pages19
JournalJournal of Medicinal Chemistry
Issue number8
Publication statusPublished - 19 Apr 2007
Externally publishedYes

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