{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:19:12Z","timestamp":1790273952469,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,11,24]],"date-time":"2026-11-24T00:00:00Z","timestamp":1795478400000},"content-version":"am","delay-in-days":327,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM133421"],"award-info":[{"award-number":["R35GM133421"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007088","name":"Jagiellonian University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre Poland","doi-asserted-by":"publisher","award":["2019\/33\/B\/NZ7\/02822"],"award-info":[{"award-number":["2019\/33\/B\/NZ7\/02822"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH133849"],"award-info":[{"award-number":["R01MH133849"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000009","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":[[2026,1]]},"DOI":"10.1016\/j.ejmech.2025.118369","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T21:58:32Z","timestamp":1763762312000},"page":"118369","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"P3","title":["Fine-tuning 5-HT7 receptor selectivity, inverse agonism, and metabolic stability of new (aryloxy)ethyl-piperidines toward antidepressant and pro-cognitive properties"],"prefix":"10.1016","volume":"302","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7940-9500","authenticated-orcid":false,"given":"Vittorio","family":"Canale","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Blicharz-Futera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Bijata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie G.","family":"Cavalco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Partyka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matylda","family":"Stefaniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Kami\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Sata\u0142a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawid","family":"Warszycki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle K.","family":"Lanham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Go\u0142\u0119biowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Gawlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Smolik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystian","family":"Bijata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Jastrz\u0119bska-Wi\u0119sek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"Kurczab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej J.","family":"Bojarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Walczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"McCorvy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"W\u0142odarczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Popik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Zajdel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.118369_bib1","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1177\/02698811231211228","article-title":"The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: a systematic review","volume":"37","author":"Gottlieb","year":"2023","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.ejmech.2025.118369_bib2","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.2147\/NDT.S68417","article-title":"The clinical utility of lurasidone in schizophrenia: patient considerations","volume":"11","author":"Harvey","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"10.1016\/j.ejmech.2025.118369_bib3","doi-asserted-by":"crossref","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.ejmech.2025.118369_bib4","doi-asserted-by":"crossref","first-page":"5482","DOI":"10.1002\/alz.13090","article-title":"Amisulpride as a potential disease-modifying drug in the treatment of tauopathies","volume":"19","author":"Jahreis","year":"2023","journal-title":"Alzheimer's Dement."},{"key":"10.1016\/j.ejmech.2025.118369_bib5","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0896-6273(93)90149-L","article-title":"A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of Mammalian circadian rhythms","volume":"11","author":"Lovenberg","year":"1993","journal-title":"Neuron"},{"key":"10.1016\/j.ejmech.2025.118369_bib6","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3389\/fnbeh.2014.00306","article-title":"Cellular mechanisms of the 5-HT7 receptor-mediated signaling","volume":"8","author":"Guseva","year":"2014","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.ejmech.2025.118369_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110532","article-title":"Activation of the 5-HT7 receptor and MMP-9 signaling module in the hippocampal CA1 region is necessary for the development of depressive-like behavior","volume":"38","author":"Bijata","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.ejmech.2025.118369_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0009166","article-title":"Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections","volume":"5","author":"Domenici","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2025.118369_bib9","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1124\/jpet.112.193995","article-title":"Translational evaluation of JNJ-18038683, a 5-hydroxytryptamine type 7 receptor antagonist, on rapid eye movement sleep and in major depressive disorder","volume":"342","author":"Bonaventure","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ejmech.2025.118369_bib10","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1097\/JCP.0000000000001889","article-title":"Lack of efficacy of JNJ-18038683 on cognitive impairment in patients with stable bipolar disorder","volume":"44","author":"Arshadi","year":"2024","journal-title":"J. Clin. Psychopharmacol."},{"key":"10.1016\/j.ejmech.2025.118369_bib11","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.ejmech.2012.07.043","article-title":"The multiobjective based design, synthesis and evaluation of the arylsulfonamide\/amide derivatives of aryloxyethyl- and arylthioethyl- piperidines and pyrrolidines as a novel class of potent 5-HT7 receptor antagonists","volume":"56","author":"Zajdel","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118369_bib12","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1039\/C5MD00166H","article-title":"Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT7 receptor antagonists and their psychotropic properties","volume":"6","author":"Zajdel","year":"2015","journal-title":"Med. Chem. Commun."},{"key":"10.1016\/j.ejmech.2025.118369_bib13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbr.2018.10.004","article-title":"Novel antagonists of 5-HT(6) and\/or 5-HT(7) receptors affect the brain monoamines metabolism and enhance the anti-immobility activity of different antidepressants in rats","volume":"359","author":"Partyka","year":"2019","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.ejmech.2025.118369_bib14","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ejmech.2015.11.040","article-title":"Towards new 5-HT7 antagonists among arylsulfonamide derivatives of (Aryloxy)ethyl-alkyl amines: multiobjective based design, synthesis, and antidepressant and anxiolytic properties","volume":"108","author":"Canale","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118369_bib15","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.bmc.2017.03.057","article-title":"Novel 5-HT(7)R antagonists, arylsulfonamide derivatives of (aryloxy)propyl piperidines: add-on effect to the antidepressant activity of SSRI and DRI, and pro-cognitive profile","volume":"25","author":"Canale","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118369_bib16","doi-asserted-by":"crossref","first-page":"10958","DOI":"10.1021\/acs.joc.0c01044","article-title":"Sustainable synthesis of a potent and selective 5-HT(7) receptor antagonist using a mechanochemical approach","volume":"85","author":"Canale","year":"2020","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2025.118369_bib17","doi-asserted-by":"crossref","first-page":"16156","DOI":"10.1021\/acssuschemeng.3c04023","article-title":"Multistep mechanochemical synthesis of PZ-1190, a multitarget antipsychotic agent","volume":"11","author":"Canale","year":"2023","journal-title":"ACS Sustain. Chem. Eng."},{"key":"10.1016\/j.ejmech.2025.118369_bib18","doi-asserted-by":"crossref","first-page":"13279","DOI":"10.1021\/acs.jmedchem.1c00224","article-title":"Structure-based design and optimization of FPPQ, a dual-acting 5-HT(3) and 5-HT(6) receptor antagonist with antipsychotic and procognitive properties","volume":"64","author":"Zajdel","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118369_bib19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/7355_2013_29","article-title":"The influence of bioisosteres in drug design: tactical applications to address developability problems","volume":"9","author":"Meanwell","year":"2015","journal-title":"tactics in contemporary drug design"},{"key":"10.1016\/j.ejmech.2025.118369_bib20","series-title":"Proceedings of the ACM\/IEEE Conference on Supercomputing (SC06)","article-title":"Scalable algorithms for molecular dynamics simulations on commodity clusters","author":"Bowers","year":"2006"},{"key":"10.1016\/j.ejmech.2025.118369_bib21","series-title":"Molecular Discovery; Program","year":"2020"},{"key":"10.1016\/j.ejmech.2025.118369_bib22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1124\/jpet.110.167346","article-title":"Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity","volume":"334","author":"Ishibashi","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ejmech.2025.118369_bib23","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1021\/acschemneuro.4c00480","article-title":"Guanidine derivative ADS1017, a potent histamine H3 receptor antagonist with promising analgesic activity and satisfactory safety profile","volume":"15","author":"Karcz","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.ejmech.2025.118369_bib24","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2025.118369_bib25","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1021\/acs.jctc.3c00044","article-title":"Epik: pk(a) and protonation state prediction through machine learning","volume":"19","author":"Johnston","year":"2023","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.ejmech.2025.118369_bib26","doi-asserted-by":"crossref","first-page":"7106","DOI":"10.1021\/acs.jctc.1c00810","article-title":"Efficient exploration of chemical space with docking and deep learning","volume":"17","author":"Yang","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.ejmech.2025.118369_bib27","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118369_bib28","doi-asserted-by":"crossref","first-page":"8717","DOI":"10.1021\/acs.jmedchem.8b00828","article-title":"Amino acid hot spots of halogen bonding: a combined theoretical and experimental case study of the 5-HT(7) receptor","volume":"61","author":"Kurczab","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118369_bib29","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/acschemneuro.1c00061","article-title":"2-Phenyl-1H-pyrrole-3-carboxamide as a new scaffold for developing 5-HT(6) receptor inverse agonists with cognition-enhancing activity","volume":"12","author":"Drop","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.ejmech.2025.118369_bib30","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1016\/0006-2952(73)90196-2","article-title":"Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction","volume":"22","author":"Cheng","year":"1973","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.118369_bib31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2157-7609.1000126","article-title":"Comparative in-vitro intrinsic clearance of imipramine in multiple species liver microsomes: human, rat, mouse and dog","volume":"3","author":"Singh","year":"2012","journal-title":"J. Drug Metab. Toxicol."},{"key":"10.1016\/j.ejmech.2025.118369_bib32","doi-asserted-by":"crossref","DOI":"10.3390\/biom13010012","article-title":"1-(Arylsulfonyl-isoindol-2-yl)piperazines as 5-HT(6)R antagonists: mechanochemical synthesis, in vitro pharmacological properties and glioprotective activity","volume":"13","author":"Canale","year":"2022","journal-title":"Biomolecules"},{"key":"10.1016\/j.ejmech.2025.118369_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112203","article-title":"A non-hallucinogenic LSD analog with therapeutic potential for mood disorders","volume":"42","author":"Lewis","year":"2023","journal-title":"Cell Rep."},{"key":"10.1016\/j.ejmech.2025.118369_bib34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S1056-8719(02)00166-1","article-title":"The power issue: determination of KB or Ki from IC50. A closer look at the cheng-prusoff equation, the schild plot and related power equations","volume":"46","author":"Cheng","year":"2001","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"10.1016\/j.ejmech.2025.118369_bib35","first-page":"327","article-title":"Behavioral despair in mice: a primary screening test for antidepressants","volume":"229","author":"Porsolt","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"10.1016\/j.ejmech.2025.118369_bib36","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00213-014-3738-4","article-title":"1-aminocyclopropanecarboxylic acid (ACPC) produces procognitive but not antipsychotic-like effects in rats","volume":"232","author":"Popik","year":"2015","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1016\/j.ejmech.2025.118369_bib37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0166-4328(88)90157-X","article-title":"A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data","volume":"31","author":"Ennaceur","year":"1988","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.ejmech.2025.118369_bib38","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0087293","article-title":"Evaluating strategies to normalise biological replicates of Western blot data","volume":"9","author":"Degasperi","year":"2014","journal-title":"PLoS One"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425011341?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425011341?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:20:12Z","timestamp":1773818412000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425011341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":38,"alternative-id":["S0223523425011341"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118369","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Fine-tuning 5-HT7 receptor selectivity, inverse agonism, and metabolic stability of new (aryloxy)ethyl-piperidines toward antidepressant and pro-cognitive properties","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118369","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":"118369"}}