In 2017,Garcia-Carceles, Javier; Decara, Juan M.; Vazquez-Villa, Henar; Rodriguez, Ramon; Codesido, Eva; Cruces, Jacobo; Brea, Jose; Loza, Maria I.; Alen, Francisco; Botta, Joaquin; McCormick, Peter J.; Ballesteros, Juan A.; Benhamu, Bellinda; Rodriguez de Fonseca, Fernando; Lopez-Rodriguez, Maria L. published 《A Positive Allosteric Modulator of the Serotonin 5-HT2C Receptor for Obesity》.Journal of Medicinal Chemistry published the findings.Formula: C6H7Br2N The information in the text is summarized as follows:
The 5-HT2CR agonist lorcaserin, clin. approved for the treatment of obesity, causes important side effects mainly related to subtype selectivity. In the search for 5-HT2CR allosteric modulators as safer antiobesity drugs, a chem. library from Vivia Biotech was screened using ExviTech platform. Structural modifications of identified hit VA240 in synthesized analogs 6-41 afforded compound 11 (N-[(1-benzyl-1H-indol-3-yl)methyl]pyridin-3-amine, VA012), which exhibited dose-dependent enhancement of serotonin efficacy, no significant off-target activities, and low binding competition with serotonin or other orthosteric ligands. PAM 11 was very active in feeding inhibition in rodents, an effect that was not related to the activation of 5-HT2AR. A combination of 11 with the SSRI sertraline increased the anorectic effect. Subchronic administration of 11 reduced food intake and body weight gain without causing CNS-related malaise. The behavior of compound 11 identified in this work supports the interest of a serotonin 5-HT2CR PAM as a promising therapeutic approach for obesity. In the experiment, the researchers used many compounds, for example, 2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8Formula: C6H7Br2N)
2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8) belongs to pyridine. Pyridine is widely used in the precursor to agrochemicals and pharmaceuticals. Also, it is used as an important reagent and organic solvent.Formula: C6H7Br2N