New ligands of the ghrelin receptor based on the 1,2,4-triazole scaffold by introduction of a second chiral center

Mathieu Maingot (1) , Anne-Laure Blayo (1) , Severine Denoyelle (1) , Céline M’kadmi (1) , Marjorie Damian (1) , Sophie Mary (1) , Didier Gagne (1) , Pierre Sanchez (1) , Babette Aicher (2) , Peter Schmidt (2) , Gilbert Müller (2) , Michael Teifel (2) , Eckhard Günther (2) , Jacky Marie (1) , Jean-Louis Banères (1) , Jean Martinez (1) , Jean-Alain Fehrentz (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 Aeterna-Zentaris

Introducing a second chiral center on our previously described 1,2,4-triazole, allowed us to increase diversity and elongate the 'C-terminal part' of the molecule. Therefore, we were able to explore mimics of the substance P analogs described as inverse agonists. Some compounds presented affinities in the nanomolar range and potent biological activities, while one exhibited a partial inverse agonist behavior similar to a Substance P analog.

Mots clés: Antagonist; Chirality; Ghrelin receptor (GHS-R1a); Inverse agonist; Structural modulation; 1 2 4-Triazole scaffold

Domaines: Chimie thérapeutique

Mathieu Maingot, Anne-Laure Blayo, Severine Denoyelle, Céline M’kadmi, Marjorie Damian, et al.. New ligands of the ghrelin receptor based on the 1,2,4-triazole scaffold by introduction of a second chiral center. Bioorganic and Medicinal Chemistry Letters, 2016, 26 (10), pp.2408-2412. ⟨10.1016/j.bmcl.2016.04.003⟩. ⟨hal-02871896⟩