2026-07-23T00:55:59Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1139552025-03-18T13:06:15Zcom_20.500.14352_14col_20.500.14352_15

Marco, Isabel Valhondo Falcón, Margarita Martín-Fontecha Corrales, María Del Mar Vázquez Villa, María Del Henar Del Rio, Joaquin Planas, Anna Sagredo Ezquioga, Onintza Ramos Atance, José Antonio Torrecillas, Iván R. Pardo, Leonardo Frechilla, Diana Benhamú Salama, Bellinda López Rodríguez, María Luz 2025-01-13T12:38:49Z 2025-01-13T12:38:49Z 2011-12-08 Marco, I., Valhondo, M., Martı́n-Fontecha, M., Vázquez-Villa, H., Del Rı́o, J., Planas, A., Sagredo, O., Ramos, J. A., Torrecillas, I. R., Pardo, L., Frechilla, D., Benhamú, B., López-Rodrı́guez, M. L. New Serotonin 5-HT1A Receptor Agonists with Neuroprotective Effect against Ischemic Cell Damage. J. Med. Chem. 2011, 54 (23), 7986-7999 0022-2623 10.1021/jm2007886 https://hdl.handle.net/20.500.14352/113955 1520-4804 https://doi.org/10.1021/jm2007886 https://pubs.acs.org/doi/10.1021/jm2007886 We report the synthesis of new compounds 4–35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT1A receptor (5-HT1AR). Computational β2-based homology models of the ligand–receptor complexes were used to explain the observed structure–affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT1AR agonist (Ki = 5.9 nM, EC50 = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats. eng http://creativecommons.org/licenses/by-nc-nd/4.0/ restricted access Attribution-NonCommercial-NoDerivatives 4.0 International New serotonin 5-HT1A receptor agonists with neuroprotective effect against ischemic cell damage journal article