{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:08:57Z","timestamp":1783033737725,"version":"3.54.6"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T00:00:00Z","timestamp":1445990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005969","name":"University of Bologna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005969","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian Ministry for Education, Universities and Research (MIUR)"},{"name":"Unirimini"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2016,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) is a major public health challenge that faces an aging global population. Current drug treatment has demonstrated only symptomatic efficacy, leaving an unmet medical need for a new generation of disease\u2010modifying therapies. Following the multitarget\u2010directed ligand approach, a small library of coumarin\u2010based derivatives was designed and synthesized as a follow\u2010up to our studies on AP2238, aimed at expanding its biological profile. The coumarin substitution pattern at the 6\u2010 or 7\u2010position was modified by introducing alkyl chains of variable lengths and with different terminal amino functional groups. 3\u2010(4\u2010{[Benzyl(ethyl)amino]methyl}phenyl)\u20106\u2010({5\u2010[(7\u2010methoxy\u20106<jats:italic>H<\/jats:italic>\u2010indeno[2,1\u2010<jats:italic>b<\/jats:italic>]quinolin\u201011\u2010yl)amino]pentyl}oxy)\u20102<jats:italic>H<\/jats:italic>\u2010chromen\u20102\u2010one, bearing the bulkiest amine, emerged as a non\u2010neurotoxic dual acetylcholinesterase (AChE)\/butyrylcholinesterase (BuChE) inhibitor, potentially suitable for the treatment of the middle stage of AD. Furthermore, the introduction of a diethylamino spacer, as in 3\u2010(4\u2010{[benzyl(ethyl)amino]methyl}phenyl)\u20106\u2010{[5\u2010(diethylamino)pentyl]oxy}\u20102<jats:italic>H<\/jats:italic>\u2010chromen\u20102\u2010one and 3\u2010(4\u2010{[benzyl(ethyl)amino]methyl}phenyl)\u20107\u2010[4\u2010(diethylamino)butoxy]\u20102<jats:italic>H<\/jats:italic>\u2010chromen\u20102\u2010one, led to nanomolar human AChE inhibitors endowed with significant inhibitory activity toward A\u03b2<jats:sub>42<\/jats:sub> self\u2010aggregation, whereas the reference compound was completely ineffective. Furthermore, 3\u2010(4\u2010{[benzyl(ethyl)amino]methyl}phenyl)\u20107\u2010[4\u2010(diethylamino)butoxy]\u20102<jats:italic>H<\/jats:italic>\u2010chromen\u20102\u2010one also showed promising neuroprotective behavior, which makes it a potential candidate for development into a disease\u2010modifying agent.<\/jats:p>","DOI":"10.1002\/cmdc.201500392","type":"journal-article","created":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T08:24:11Z","timestamp":1446020651000},"page":"1296-1308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Multitarget Strategy to Address Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and Computational Studies of Coumarin\u2010Based Derivatives"],"prefix":"10.1002","volume":"11","author":[{"given":"Serena","family":"Montanari","sequence":"first","affiliation":[{"name":"Department of Pharmacy &amp; Biotechnology, Alma Mater Studiorum University of Bologna  Via Belmeloro\u20056 40126 Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; 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