RT Journal Article
T1 A new serotonin 5-HT 6 receptor antagonist with procognitive activity - Importance of a halogen bond interaction to stabilize the binding
A1 González Vera, Juan Antonio
A1 Medina Muñoz, Rocío Almudena
A1 Martín-Fontecha Corrales, María Del Mar
A1 Gonzalez Wong, Ángel
A1 Fuente Mendizábal, Tania de la
A1 Vázquez Villa, María Del Henar
A1 García Cárceles, Javier
A1 Botta, Joaquín
A1 McCormick, Peter J.
A1 Benhamú Salama, Bellinda
A1 Pardo Carrasco, Leonardo
A1 López Rodríguez, María Luz
AB 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.
PB Nature Publishing Group
SN 2045-2322
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/18265
UL https://hdl.handle.net/20.500.14352/18265
LA eng
NO received: 01 August 2016accepted: 16 December 2016Published: 24 January 2017
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
NO European COST Action CM1207 (GLISTEN)
DS Docta Complutense
RD 18 dic 2025