Name: 2-Cyano-2-methylpropanoic acid. The mechanism of aromatic electrophilic substitution of aromatic heterocycles is consistent with that of benzene. Compound: 2-Cyano-2-methylpropanoic acid, is researched, Molecular C5H7NO2, CAS is 22426-30-8, about Development of Nonpeptidic Inverse Agonists of the Ghrelin Receptor (GHSR) Based on the 1,2,4-Triazole Scaffold. Author is Haj Salah, Khoubaib Ben; Maingot, Mathieu; Blayo, Anne-Laure; M’Kadmi, Celine; Damian, Marjorie; Mary, Sophie; Cantel, Sonia; Neasta, Jeremie; Oiry, Catherine; Peraldi-Roux, Sylvie; Fernandez, Gimena; Romero, Guadalupe Garcia; Perello, Mario; Marie, Jacky; Baneres, Jean-Louis; Fehrentz, Jean-Alain; Denoyelle, Severine.
GHSR controls, among others, growth hormone and insulin secretion, adiposity, feeding, and glucose metabolism Therefore, an inverse agonist ligand capable of selectively targeting GHSR and reducing its high constitutive activity appears to be a good candidate for the treatment of obesity-related metabolic diseases. In this context, we present a study that led to the development of several highly potent and selective inverse agonists of GHSR based on the 1,2,4-triazole scaffold. We demonstrate that, depending on the nature of the substituents on positions 3, 4, and 5, this scaffold leads to ligands that exert an intrinsic inverse agonist activity on GHSR-catalyzed G protein activation through the stabilization of a specific inactive receptor conformation. Thanks to an in vivo evaluation, we also show that one of the most promising ligands, compound I, not only exerts an effect on insulin secretion in rat pancreatic islets but also affects the orexigenic effects of ghrelin in mice.
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