Alonso, DulceVázquez Villa, María Del HenarGamo, Ana M.Martínez Esperón, Maria F.Tortosa, MariolaViso, AlmaFernández de la Pradilla, RobertoJunquera González, María ElenaAicart Sospedra, EmilioMartín-Fontecha Corrales, María Del MarBenhamú Salama, BellindaLópez Rodríguez, María LuzOrtega Gutiérrez, Silvia2025-01-152025-01-152010-09-01Alonso, D., Vázquez-Villa, H., Gamo, A. M., Martínez-Esperón, M. F., Tortosa, M., Viso, A., de la Pradilla, R.F., Junquera, E., Aicart, E. ; Martín-Fontecha, M., Benhamú, B., López-Rodríguez, M. L., Ortega-Gutiérrez, S. Development of Fluorescent Ligands for the Human 5-HT1A Receptor. ACS Med. Chem. Lett. 2010, 1 (6), 249-2531948-587510.1021/ml100053yhttps://hdl.handle.net/20.500.14352/114435In this work, we report the design and synthesis of a set of fluorescent probes targeting the human 5-HT1A receptor (h5-HT1AR). Among the synthesized compounds, derivative 4 deserves special attention as being a high-affinity ligand (Ki = 2 nM) with good fluorescent properties (Iem > 1000 au and a fluorescence quantum yield, Φf, of 0.26), which enables direct observation of the h5-HT1AR in cells. Thus, it represents the first efficacious fluorescent probe for the specific labeling of h5-HT1AR in cells. Our results provide the basis for the introduction of a variety of tags in scaffolds of G protein-coupled receptor (GPCR) ligands that enable visualization, covalent binding, or affinity pull-down of receptors. These strategies should contribute to the optimization of the therapeutic exploitation of known or new members of the GPCR superfamily by providing valuable information about their location or level of expression.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1021/ml100053yhttps://pubs.acs.org/doi/10.1021/ml100053yrestricted access547GPCRSerotonin 5-HT1A receptorFluorescent probesReceptor visualizationQuímica orgánica (Química)2306 Química Orgánica2390.01 Diseño. Síntesis y Estudio Nuevos Fármacos