{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:55:07Z","timestamp":1792068907811,"version":"4.4.0"},"reference-count":28,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2027,1]]},"DOI":"10.1016\/j.bmcl.2026.130788","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:50:11Z","timestamp":1790783411000},"page":"130788","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Synthesis and pharmacological evaluation of a series of fluoro-substituted 3-phenoxy-azetidines as cortical enhancers for the treatment of apathy"],"prefix":"10.1016","volume":"142","author":[{"given":"Clas","family":"Sonesson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sverker","family":"von Unge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gullme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Rousk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fagerberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ther\u00e9se","family":"Knubbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boel","family":"Svanberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Ljung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Hjorth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2026.130788_bb0005","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.bmcl.2026.130788_bb0010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2018.08.004","article-title":"\u201cPure apathy\u201d and cognitive dysfunctions in Parkinson\u2019s disease: a meta-analytic study","volume":"94","author":"D\u2019Iorio","year":"2018","journal-title":"Neurosci Biobehav Rev"},{"key":"10.1016\/j.bmcl.2026.130788_bb0015","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jagp.2020.04.026","article-title":"Neurobiologic rationale for treatment of apathy in Alzheimer\u2019s disease with methylphenidate","volume":"29","author":"van Dyck","year":"2021","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.1016\/j.bmcl.2026.130788_bb0020","doi-asserted-by":"crossref","DOI":"10.12786\/bn.2025.18.e4","article-title":"Efficacy of methylphenidate in patients with brain disease: a systematic review and meta-analysis","volume":"18","author":"Park","year":"2025","journal-title":"Brain Neurorehabil"},{"key":"10.1016\/j.bmcl.2026.130788_bb0025","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1176\/appi.ajp.2017.17030316","article-title":"Methylphenidate for apathy in community dwelling older veterans with mild Alzheimer\u2019s disease: a double-blind, randomized, placebo-controlled trial","volume":"175","author":"Padala","year":"2018","journal-title":"Am J Psychiatry"},{"key":"10.1016\/j.bmcl.2026.130788_bb0030","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.biopsych.2006.04.022","article-title":"Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function","volume":"60","author":"Berridge","year":"2006","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.bmcl.2026.130788_bb0035","doi-asserted-by":"crossref","unstructured":"Zhu J, Reith MEA. Role of dopamine transporter in the action of psychostimulants, nicotine, and other drugs of abuse: CNS Neurol Disord Drug Targets 2008;7:393\u2013409. doi:https:\/\/doi.org\/10.2174\/187152708786927877.","DOI":"10.2174\/187152708786927877"},{"key":"10.1016\/j.bmcl.2026.130788_bb0040","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/B978-0-12-420118-7.00004-4","article-title":"Monoamine transporter inhibitors and substrates as treatments for stimulant abuse","volume":"69","author":"Howell","year":"2014","journal-title":"Adv Pharmacol"},{"key":"10.1016\/j.bmcl.2026.130788_bb0045","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1124\/jpet.120.000037","article-title":"(3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752) \u2014 a novel cortical-preferring catecholamine transmission- and cognition-promoting agent","volume":"374","author":"Hjorth","year":"2020","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.bmcl.2026.130788_bb0050","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1002\/cpdd.959","article-title":"First-in-human study to assess the safety, tolerability, and pharmacokinetics of Pirepemat, a cortical enhancer, in healthy volunteers","volume":"10","author":"Rein-Hedin","year":"2021","journal-title":"Clin Pharmacol Drug Dev"},{"key":"10.1016\/j.bmcl.2026.130788_bb0055","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1002\/mds.28020","article-title":"A phase 2a trial investigating the safety and tolerability of the novel cortical enhancer IRL752 in Parkinson\u2019s disease dementia","volume":"35","author":"Svenningsson","year":"2020","journal-title":"Mov Disord"},{"key":"10.1016\/j.bmcl.2026.130788_bb0060","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.parkreldis.2019.04.007","article-title":"Involvement of cortical dysfunction in frequent falls in patients with Parkinson\u2019s disease","volume":"64","author":"Otomune","year":"2019","journal-title":"Parkinsonism Relat Disord"},{"key":"10.1016\/j.bmcl.2026.130788_bb0065","first-page":"467","article-title":"Influence of serotonin 5-HT7 receptor blockade on the behavioral and neurochemical effects of imipramine in rats","volume":"60","author":"Weso\u0142owska","year":"2008","journal-title":"Pharmacol Rep"},{"key":"10.1016\/j.bmcl.2026.130788_bb0070","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1021\/acschemneuro.8b00283","article-title":"Pharmacology and therapeutic potential of the 5-HT7 receptor","volume":"10","author":"Blattner","year":"2019","journal-title":"ACS Chem Neurosci"},{"key":"10.1016\/j.bmcl.2026.130788_bb0075","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1177\/0269881118798612","article-title":"Differential \u03b12A- and \u03b12C-adrenoceptor protein expression in presynaptic and postsynaptic density fractions of postmortem human prefrontal cortex","volume":"33","author":"Erdozain","year":"2019","journal-title":"Journal of psychopharmacology (Oxford, England)"},{"key":"10.1016\/j.bmcl.2026.130788_bb0080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fpsyt.2017.00144","article-title":"Therapeutic potential of selectively targeting the \u03b12C-adrenoceptor in cognition, depression, and schizophrenia-new developments and future perspective","volume":"8","author":"Uys","year":"2017","journal-title":"Front Psychiatry"},{"key":"10.1016\/j.bmcl.2026.130788_bb0085","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1021\/acschemneuro.6b00371","article-title":"In vivo systems response profiling and multivariate classification of CNS active compounds: a structured tool for CNS drug discovery","volume":"8","author":"Waters","year":"2017","journal-title":"ACS Chem Neurosci"},{"key":"10.1016\/j.bmcl.2026.130788_bb0090","unstructured":"Sonesson C, Pettersson F. Patent application WO 2018\/091687 A1 (Priority date: November 18, 2016)."},{"key":"10.1016\/j.bmcl.2026.130788_bb0095","unstructured":"Kaza\u0109onoka G, Ekawa B, Fernandez A, Buksa M, Nguyen L, Waters N. Patent application WO 2025\/008504 A1 (Priority date: July 6, 2023)."},{"key":"10.1016\/j.bmcl.2026.130788_bb0100","unstructured":"Waters N. Patent application WO 2025\/008506 A1 (Priority date: July 6, 2023)."},{"key":"10.1016\/j.bmcl.2026.130788_bb0105","unstructured":"Peters D, Olsen GM, Nielsen E\u00d8, Scheel-Kr\u00fcger J. Patent application WO 2004\/113297 A2 (Priority date: June 24, 2003)."},{"key":"10.1016\/j.bmcl.2026.130788_bb0110","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0149-7634(98)00020-7","article-title":"D-amphetamine, cocaine and caffeine: a comparative study of acute effects on locomotor activity and behavioural patterns in rats","volume":"23","author":"Antoniou","year":"1998","journal-title":"Neurosci Biobehav Rev"},{"key":"10.1016\/j.bmcl.2026.130788_bb0115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fpsyt.2024.1508732","article-title":"Methylphenidate abuse and misuse in patients affected with a psychiatric disorder and a substance use disorder: a systematic review","volume":"15","author":"Chiappini","year":"2024","journal-title":"Front Psychiatry."},{"key":"10.1016\/j.bmcl.2026.130788_bb0120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2210-6-6","article-title":"Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs","volume":"6","author":"Han","year":"2006","journal-title":"BMC Pharmacol"},{"key":"10.1016\/j.bmcl.2026.130788_bb0125","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s40263-015-0236-0","article-title":"Targeting the serotonin 5-HT7 receptor in the search for treatments for CNS disorders: rationale and Progress to date","volume":"29","author":"Nikiforuk","year":"2015","journal-title":"CNS Drugs"},{"key":"10.1016\/j.bmcl.2026.130788_bb0130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fpsyt.2021.623684","article-title":"Current limitations and candidate potential of 5-HT7 receptor antagonism in psychiatric pharmacotherapy","volume":"12","author":"Okubo","year":"2021","journal-title":"Front Psychiatry"},{"key":"10.1016\/j.bmcl.2026.130788_bb0135","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00044-021-02797-4","article-title":"Design and discovery of a high affinity, selective and \u03b2-Arrestin biased 5-HT7 receptor agonist","volume":"31","author":"Onyameh","year":"2022","journal-title":"Med Chem Res"},{"key":"10.1016\/j.bmcl.2026.130788_bb0140","unstructured":"EUCT number: 2024\u2013511426\u201331-00. Protocol code: IRL757C001. https:\/\/euclinicaltrials.eu\/search-for-clinical-trials\/?lang=en&EUCT=2024-511426-31-00."}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X26002556?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X26002556?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:36:37Z","timestamp":1792067797000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X26002556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2027,1]]},"references-count":28,"alternative-id":["S0960894X26002556"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2026.130788","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2027,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis and pharmacological evaluation of a series of fluoro-substituted 3-phenoxy-azetidines as cortical enhancers for the treatment of apathy","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2026.130788","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"130788"}}