2026-06-28T09:48:49Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/182652025-01-20T17:10:00Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc González Vera, Juan Antonio author Medina Muñoz, Rocío Almudena author Martín-Fontecha Corrales, María Del Mar author Gonzalez Wong, Ángel author Fuente Mendizábal, Tania de la author Vázquez Villa, María Del Henar author García Cárceles, Javier author Botta, Joaquín author McCormick, Peter J. author Benhamú Salama, Bellinda author Pardo Carrasco, Leonardo author López Rodríguez, María Luz author 2017 Serotonin 5-HT 6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer's disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT 6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT 6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT 6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT 2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit. 2045-2322 10.1038/srep41293 https://hdl.handle.net/20.500.14352/18265 http://dx.doi.org/10.1038/srep41293 https://www.nature.com/articles/srep41293 A new serotonin 5-HT 6 receptor antagonist with procognitive activity - Importance of a halogen bond interaction to stabilize the binding