{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T13:01:19Z","timestamp":1793970079623,"version":"4.8.0"},"reference-count":58,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22077091"],"award-info":[{"award-number":["22077091"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2023NSFSC0605"],"award-info":[{"award-number":["2023NSFSC0605"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.ejmech.2025.118437","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:33:28Z","timestamp":1764808408000},"page":"118437","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Benzylpiperidine-pyridazin-3(2H)-one derivatives as potential multifunctional agents against Alzheimer's disease"],"prefix":"10.1016","volume":"303","author":[{"given":"Yichun","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqin","family":"Cong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxiu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghuai","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6565-6073","authenticated-orcid":false,"given":"Yong","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.118437_bib1","first-page":"3907","article-title":"Recent advances in Alzheimer's disease: mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.ejmech.2025.118437_bib2","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1080\/13543784.2016.1216972","article-title":"Old and new acetylcholinesterase inhibitors for Alzheimer's disease","volume":"25","author":"Galimberti","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.ejmech.2025.118437_bib3","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer's disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"10.1016\/j.ejmech.2025.118437_bib4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41582-021-00557-x","article-title":"Can we learn lessons from the FDA's approval of aducanumab?","volume":"17","author":"Liu","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.ejmech.2025.118437_bib5","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/s41573-022-00391-w","article-title":"The amyloid hypothesis in alzheimer disease: new insights from new therapeutics","volume":"21","author":"Karran","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2025.118437_bib6","article-title":"Alzheimer\u2019s disease drug development pipeline: 2023","volume":"9","author":"Cummings","year":"2023","journal-title":"Alzheimer\u2019s Dement"},{"key":"10.1016\/j.ejmech.2025.118437_bib7","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer disease: an update on pathobiology and treatment strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell."},{"key":"10.1016\/j.ejmech.2025.118437_bib8","doi-asserted-by":"crossref","first-page":"9305","DOI":"10.3390\/ijms23169305","article-title":"Symptomatic and disease-modifying therapy pipeline for alzheimer's disease: towards a personalized polypharmacology patient-centered approach","volume":"23","author":"Morat\u00f3","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2025.118437_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.neubiorev.2023.105192","article-title":"New perspectives on the basal forebrain cholinergic system in Alzheimer's disease","volume":"150","author":"Berry","year":"2023","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.ejmech.2025.118437_bib10","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1093\/brain\/awad159","article-title":"The amyloid Cascade hypothesis: an updated critical review","volume":"146","author":"Kepp","year":"2023","journal-title":"Brain"},{"key":"10.1016\/j.ejmech.2025.118437_bib11","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1089\/ars.2020.8134","article-title":"Preventive and therapeutic strategies in alzheimer's disease: focus on oxidative stress, redox metals, and ferroptosis","volume":"34","author":"Plascencia-Villa","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.ejmech.2025.118437_bib12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","article-title":"Neuroinflammation in alzheimer disease","volume":"25","author":"Heneka","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejmech.2025.118437_bib13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature11691","article-title":"Automated design of ligands to polypharmacological profiles","volume":"492","author":"Besnard","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2025.118437_bib14","doi-asserted-by":"crossref","first-page":"10581","DOI":"10.1021\/acs.jmedchem.1c00683","article-title":"Rational multitargeted drug design strategy from the perspective of a medicinal chemist","volume":"64","author":"Li","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib15","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1021\/acs.jmedchem.8b00760","article-title":"Polypharmacology by design: a medicinal chemist's perspective on multitargeting compounds","volume":"62","author":"Proschak","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.114098","article-title":"Development of novel 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives as balanced multifunctional agents against alzheimer's disease","volume":"230","author":"Shi","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib17","doi-asserted-by":"crossref","first-page":"10282","DOI":"10.1021\/jm300871x","article-title":"Structures of human acetylcholinesterase in complex with pharmacologically important ligands","volume":"55","author":"Cheung","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib18","doi-asserted-by":"crossref","first-page":"5823","DOI":"10.1021\/acs.jmedchem.6b00426","article-title":"Benzylpiperidine-linked diarylthiazoles as potential anti-alzheimer's agents: synthesis and biological evaluation","volume":"59","author":"Shidore","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2021.116074","article-title":"Novel 3-benzylidene\/benzylphthalide mannich base derivatives as potential multifunctional agents for the treatment of alzheimer's disease","volume":"35","author":"Cao","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib20","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ejmech.2016.07.052","article-title":"Rational modification of donepezil as multifunctional acetylcholinesterase inhibitors for the treatment of alzheimer's disease","volume":"123","author":"Wang","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib21","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1021\/acs.jmedchem.0c01863","article-title":"Kinetics-driven drug design strategy for next-generation acetylcholinesterase inhibitors to clinical candidate","volume":"64","author":"Zhou","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib22","doi-asserted-by":"crossref","first-page":"7942","DOI":"10.1016\/j.tet.2016.10.022","article-title":"Synthesis of 4-alkylsulfanyl phthalazin-1(2H)-ones via palladium catalyzed sulfanylation of substituted 4-bromo phthalazin-1(2H)-ones","volume":"72","author":"Malinowski","year":"2016","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2025.118437_bib23","first-page":"465","article-title":"A poly (ethylene glycol) supported chiral auxiliary for asymmetric michael reactions","volume":"3","author":"Kreidler","year":"2005","journal-title":"Synlett"},{"key":"10.1016\/j.ejmech.2025.118437_bib24","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.bmcl.2014.02.049","article-title":"Design, synthesis, and characterization of novel, nonquaternary reactivators of GF-inhibited human acetylcholinesterase","volume":"24","author":"Mchardy","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2025.118437_bib25","series-title":"Process for Preparing 3-chloro-6-(2-hydroxyphenyl)-pyridazines","author":"Bing","year":"1982"},{"key":"10.1016\/j.ejmech.2025.118437_bib26","doi-asserted-by":"crossref","first-page":"6280","DOI":"10.1021\/jm8005405","article-title":"3-amino-7-phthalazinylbenzoisoxazoles as a novel class of potent, selective, and orally available inhibitors of p38\u03b1mitogen-activated protein kinase","volume":"51","author":"Pettus","year":"2008","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib27","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1002\/asia.200700182","article-title":"The mitsunobu reaction: origin, mechanism, improvements, and applications","volume":"2","author":"But","year":"2007","journal-title":"Chem. Asian J."},{"key":"10.1016\/j.ejmech.2025.118437_bib28","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.bbrc.2007.01.186","article-title":"Dialkyl phenyl phosphates as novel selective inhibitors of butyrylcholinesterase","volume":"355","author":"Law","year":"2007","journal-title":"Biochem. Bioph. Res. Co."},{"key":"10.1016\/j.ejmech.2025.118437_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/jm0255668","article-title":"Specific targeting of acetylcholinesterase and butyrylcholinesterase recognition sites. Rational design of novel, selective, and highly potent cholinesterase inhibitors","volume":"46","author":"Savini","year":"2003","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib30","doi-asserted-by":"crossref","first-page":"10030","DOI":"10.1021\/acs.jmedchem.0c01129","article-title":"Discovery and biological evaluation of a novel highly potent selective butyrylcholinesterase inhibitor","volume":"63","author":"Li","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.104895","article-title":"Design, synthesis, and in vitro evaluation of 4-aminoalkyl-1(2H)-phthalazinones as potential multifunctional anti-alzheimer\u2019s disease agents","volume":"111","author":"Ye","year":"2021","journal-title":"Bioorganic Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib32","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.bioorg.2019.03.043","article-title":"Design, synthesis and evaluation of chalcone mannich base derivatives as multifunctional agents for the potential treatment of Alzheimer's disease","volume":"87","author":"Zhang","year":"2019","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib33","doi-asserted-by":"crossref","first-page":"9089","DOI":"10.1021\/jm401047q","article-title":"Synthesis and evalution of multi-target-directed ligands against alzheimer disease based on the fusion of donepezil and ebselen","volume":"56","author":"Luo","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib34","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.bbadis.2013.10.015","article-title":"Oxidative stress and mitochondrial dysfunction in Alzheimer's disease","volume":"1842","author":"Wang","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejmech.2025.118437_bib35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1021\/jf0305231","article-title":"Extending applicability of the oxygen radical absorbance capacity (ORAC-fluorescein) assay","volume":"52","author":"D\u00e1valos","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib36","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s40478-019-0777-4","article-title":"Soluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer's disease progression","volume":"7","author":"De","year":"2019","journal-title":"Acta. Neuropathol. Com"},{"key":"10.1016\/j.ejmech.2025.118437_bib37","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1021\/acs.accounts.9b00248","article-title":"Metal ions in alzheimer's disease: a key role or not?","volume":"52","author":"Liu","year":"2019","journal-title":"Accounts Chem. Res."},{"key":"10.1016\/j.ejmech.2025.118437_bib38","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ejmech.2014.02.045","article-title":"Design, synthesis and evaluation of genistein-O-alkylbenzylamines as potential multifunctional agents for the treatment of alzheimer's disease","volume":"76","author":"Qiang","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115216","article-title":"Discovery of novel 5-(2-hydroxyphenyl)-2-phthalide-3(3H)-pyrazolones as balanced multifunctional agents against Alzheimer\u2019s disease","volume":"250","author":"Cong","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2024.141815","article-title":"Phase behavior and interaction of strong polyelectrolyte dextran sulfate and whey protein isolation: effects of pH, protein\/polysaccharide ratio, and salt addition","volume":"464","author":"Zheng","year":"2025","journal-title":"Food Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib41","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.ejmech.2015.02.063","article-title":"Design, synthesis and evaluation of scutellarein-O-alkyl-amines as multifunctional agents for the treatment of Alzheimer's disease","volume":"94","author":"Sang","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib42","doi-asserted-by":"crossref","first-page":"105387","DOI":"10.1016\/j.bioorg.2021.105387","article-title":"Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer\u2019s disease","volume":"116","author":"Pan","year":"2021","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2022.116660","article-title":"Discovery of novel 3-butyl-6-benzyloxyphthalide mannich base derivatives as multifunctional agents against alzheimer's disease","volume":"58","author":"Liu","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib44","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0223-5234(03)00012-6","article-title":"High throughput artificial membrane permeability assay for blood\u2013brain barrier","volume":"38","author":"Di","year":"2003","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib45","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1021\/ci700257y","article-title":"Computation of octanol-water partition coefficients by guiding an additive mode with knowledge","volume":"47","author":"Cheng","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2025.118437_bib46","doi-asserted-by":"crossref","first-page":"8798","DOI":"10.1021\/acs.chemrev.7b00698","article-title":"Redox signaling by reactive electrophiles and oxidants","volume":"118","author":"Parvez","year":"2018","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2025.118437_bib47","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1021\/jf104632a","article-title":"Effect of hesperetin against oxidative stress via ER- and TrkA-Mediated actions in PC12 cells","volume":"59","author":"Hwang","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib48","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1039\/C6CS00731G","article-title":"Towards an understanding of amyloid-beta oligomers: character ization, toxicity mechanisms, and inhibitors","volume":"46","author":"Lee","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"10.1016\/j.ejmech.2025.118437_bib49","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1021\/acschemneuro.3c00576","article-title":"Small molecules N-Phenylbenzofuran-2-carboxamide and N-Phenylbenzo[b]thiophene-2-carboxamide promote beta-amyloid (A\u03b242) aggregation and mitigate neurotoxicity","volume":"14","author":"Zhao","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.ejmech.2025.118437_bib50","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00204-023-03660-8","article-title":"Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases","volume":"98","author":"Yao","year":"2024","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.ejmech.2025.118437_bib51","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.freeradbiomed.2025.05.426","article-title":"Protective effect of norepinephrine, dopamine and N-methyldopamine against chemically-induced oxidative ferroptosis in HT22 neuronal cells: protein disulfide isomerase as a mechanistic target for protection","volume":"237","author":"Hou","year":"2025","journal-title":"Free Radical Bio Med"},{"key":"10.1016\/j.ejmech.2025.118437_bib52","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neuro."},{"key":"10.1016\/j.ejmech.2025.118437_bib53","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jneumeth.2009.06.034","article-title":"A cellular model of inflammation for identifying TNF-Alpha synthesis inhibitors","volume":"2","author":"Tweedie","year":"2009","journal-title":"J. Neurosci. Meth."},{"key":"10.1016\/j.ejmech.2025.118437_bib54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jneuroim.2016.12.007","article-title":"Nitric oxide synthase inhibitor, aminoguanidine reduces intracerebroventricular colchicine induced neurodegeneration, memory impairments and changes of systemic immune responses in rats","volume":"303","author":"Sil","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.ejmech.2025.118437_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.116099","article-title":"Synthesis and evaluation of butylphthalide-scutellarein hybrids as multifunctional agents for the treatment of Alzheimer's disease","volume":"265","author":"Yu","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib56","doi-asserted-by":"crossref","first-page":"6426","DOI":"10.1007\/s12035-015-9543-1","article-title":"A, antimalarial drug artemether inhibits neuroinflammation in BV2 microglia through Nrf2-Dependent mechanisms","volume":"53","author":"Okorji","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.ejmech.2025.118437_bib57","doi-asserted-by":"crossref","first-page":"13661","DOI":"10.1021\/acs.jmedchem.5c00502","article-title":"3-Hydroxyquinolin-2-Ones act as dual inhibitors of ferroptosis and monoamine oxidase B: reducing alzheimer's disease-related amyloid PrecursorProtein and hyperphosphorylated tau in vivo","volume":"68","author":"Lv","year":"2025","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118437_bib58","doi-asserted-by":"crossref","first-page":"11693","DOI":"10.1021\/acs.jmedchem.5c00577","article-title":"Lead optimization of a butyrylcholinesterase inhibitor for the treatment of alzheimer's disease","volume":"68","author":"kosak","year":"2025","journal-title":"J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425012024?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425012024?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:54:52Z","timestamp":1781326492000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425012024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":58,"alternative-id":["S0223523425012024"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118437","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Benzylpiperidine-pyridazin-3(2H)-one derivatives as potential multifunctional agents against Alzheimer's disease","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118437","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118437"}}