2026-08-29T14:12:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/228472024-11-28T20:35:56Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967
00925njm 22002777a 4500
dc
Abas, Sonia
author
Rodriguez-Arevalo, Sergio
author
Bagan, Andrea
author
Grinan-Ferre, Christian
author
Vasilopoulou, Foteini
author
Brocos-Mosquera, Iria
author
Muguruza, Carolina
author
Perez, Belen
author
Molins, Elies
author
Javier Luque, F
author
Perez-Lozano, Pilar
author
de Jonghe, Steven
author
Daelemans, Dirk
author
Naesens, Lieve
author
Brea, Jose
author
Isabel Loza, M
author
Hernández-Hernández, Elena
author
Garcia-Sevilla, Jesus A
author
Julia Garcia-Fuster, M
author
Radan, Milica
author
Djikic, Teodora
author
Nikolic, Katarina
author
Pallas, Merce
author
Callado, Luis F
author
Escolano, Carmen
author
2020-04-09
Imidazoline I-2 receptors (I-2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I-2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of a new family of bicyclic alpha-iminophosphonates endowed with relevant affinities for human brain I-2-IR. Acute treatment in mice with a selected compound significantly decreased Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore, bicyclic alpha-iminophosphonates are tools that may open new therapeutic avenues for I-2-IR, particularly for unmet neurodegenerative conditions.
Abas Sonia, Rodriguez-Arevalo Sergio, Bagan Andrea, Grinan-Ferre Christian, Vasilopoulou Foteini, Brocos-Mosquera Iria, et al. Bicyclic alpha-Iminophosphonates as High Affinity Imidazoline I-2 Receptor Ligands for Alzheimer's Disease. J Med Chem. 2020 Apr 09;63(7):3610-3633. Epub 2020 Mar 19.
10.1021/acs.jmedchem.9b02080
1520-4804
0022-2623
Journal of Medicinal Chemistry
http://hdl.handle.net/20.500.13003/11009
32150414
L2005687973
2-s2.0-85083077827
https://hdl.handle.net/20.500.12105/22847
526405300015
Bicyclic alpha-Iminophosphonates as High Affinity Imidazoline I-2 Receptor Ligands for Alzheimer's Disease