RT Journal Article
T1 New serotonin 5-HT1A receptor agonists with neuroprotective effect against ischemic cell damage
A1 Marco, Isabel
A1 Valhondo Falcón, Margarita
A1 Martín-Fontecha Corrales, María Del Mar
A1 Vázquez Villa, María Del Henar
A1 Del Rio, Joaquin
A1 Planas, Anna
A1 Sagredo Ezquioga, Onintza
A1 Ramos Atance, José Antonio
A1 Torrecillas, Iván R.
A1 Pardo, Leonardo
A1 Frechilla, Diana
A1 Benhamú Salama, Bellinda
A1 López Rodríguez, María Luz
AB 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.
PB ACS Publications
SN 0022-2623
YR 2011
FD 2011-12-08
LK https://hdl.handle.net/20.500.14352/113955
UL https://hdl.handle.net/20.500.14352/113955
LA eng
NO 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
NO Ministería de Economía y Competetividad
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
NO Fundacion para la Investigacion Medica Aplicada FIMA
DS Docta Complutense
RD 10 abr 2025