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dc.creatorAbás, Sònia
dc.creatorRodríguez-Arévalo, Sergio
dc.creatorBagán, Andrea
dc.creatorGriñán-Ferré, Christian
dc.creatorVasilopoulou, Foteini
dc.creatorBrocos-Mosquera, Iria
dc.creatorMuguruza, Carolina
dc.creatorPérez, Belén
dc.creatorMolins, Elies
dc.creatorLuque, F. Javier
dc.creatorPérez-Lozano, Pilar
dc.creatorDe Jonghe, Steven
dc.creatorDaelemans, Dirk
dc.creatorNaesens, Lieve
dc.creatorBrea, José
dc.creatorLoza, M. Isabel
dc.creatorHernández-Hernández, Elena
dc.creatorGarcía-Sevilla, Jesús A.
dc.creatorGarcía-Fuster, M. Julia
dc.creatorRadan, Milica
dc.creatorĐikić, Teodora
dc.creatorNikolić, Katarina
dc.creatorPallàs, Mercè
dc.creatorCallado, Luis F.
dc.creatorEscolano, Carmen
dc.date.accessioned2020-05-29T10:40:07Z
dc.date.available2020-05-29T10:40:07Z
dc.date.issued2020
dc.identifier.issn0022-2623
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3576
dc.description.abstractImidazoline I2 receptors (I2-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 I2-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 α-iminophosphonates endowed with relevant affinities for human brain I2-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 α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions.en
dc.publisherAmerican Chemical Society
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172033/RS//
dc.relationMinisterio de Economı́a y Competitividad of Spain(SAF2016-77703) and the Basque Government (IT1211-19)
dc.relationSpanish Ministerio de Economı́a, Industria yCompetitividad (grant MDM-2017-0767; AEI/FEDER UE),and Generalitat de Catalunya (grant 2017SGR1746)
dc.relation.isreferencedbyhttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3768
dc.rightsrestrictedAccess
dc.sourceJournal of Medicinal Chemistry
dc.titleBicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Diseaseen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЛуqуе, Ф. Јавиер; Гриñáн-Феррé, Цхристиан; Василопоулоу, Фотеини; Броцос-Мосqуера, Ириа; Мугуруза, Царолина; Пéрез, Белéн; Молинс, Елиес; Николић, Катарина; Ђикић, Теодора; Радан, Милица; Багáн, Aндреа; Пéрез-Лозано, Пилар; Де Јонгхе, Стевен; Даелеманс, Дирк; Наесенс, Лиеве; Бреа, Јосé; Лоза, М. Исабел; Хернáндез-Хернáндез, Елена; Гарцíа-Севилла, Јесúс A.; Гарцíа-Фустер, М. Јулиа; Паллàс, Мерцè; Цалладо, Луис Ф.; Есцолано, Цармен; Aбáс, Сòниа; Родрíгуез-Aрéвало, Сергио;
dc.citation.volume63
dc.citation.issue7
dc.citation.spage3610
dc.citation.epage3633
dc.citation.rankaM21
dc.description.otherLink to erratum: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/3768]
dc.identifier.wos000526405300015
dc.identifier.doi10.1021/acs.jmedchem.9b02080
dc.identifier.scopus2-s2.0-85083077827
dc.type.versionpublishedVersion


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