{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:24:22Z","timestamp":1771482262651,"version":"3.50.1"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"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":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2023,3]]},"DOI":"10.1016\/j.ejmech.2023.115176","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T12:31:48Z","timestamp":1675686708000},"page":"115176","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Design, synthesis and biological evaluations of quinolone amides against African trypanosomiasis with improved solubility"],"prefix":"10.1016","volume":"250","author":[{"given":"Joshua","family":"Weinmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Kirchner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Engstler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz","family":"Meinel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0364-7278","authenticated-orcid":false,"given":"Ulrike","family":"Holzgrabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2023.115176_bib1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0140-6736(09)60829-1","article-title":"Human African trypanosomiasis","volume":"375","author":"Brun","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.ejmech.2023.115176_bib2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S1474-4422(12)70296-X","article-title":"Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)","volume":"12","author":"Kennedy","year":"2013","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.ejmech.2023.115176_bib3","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","article-title":"Human African trypanosomiasis","volume":"390","author":"B\u00fcscher","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.ejmech.2023.115176_bib4","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1007\/s00415-019-09425-7","article-title":"Update on human African trypanosomiasis (sleeping sickness)","volume":"266","author":"Kennedy","year":"2019","journal-title":"J. Neurol."},{"key":"10.1016\/j.ejmech.2023.115176_bib5","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1172\/JCI200421052","article-title":"Human African trypanosomiasis of the CNS: current issues and challenges","volume":"113","author":"Kennedy","year":"2004","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.ejmech.2023.115176_bib6","doi-asserted-by":"crossref","first-page":"701","DOI":"10.2174\/0929867324666170120160034","article-title":"A brief review of drug discovery research for human African trypanosomiasis","volume":"24","author":"R Cullen","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib7","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1128\/AAC.00246-11","article-title":"Antitrypanosomal activity of fexinidazole, a new oral Nitroimidazole drug candidate for treatment of sleeping sickness","volume":"55","author":"Kaiser","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115176_bib8","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s40265-019-1051-6","article-title":"Fexinidazole: first global approval","volume":"79","author":"Deeks","year":"2019","journal-title":"Drugs"},{"key":"10.1016\/j.ejmech.2023.115176_bib9","series-title":"Efficacy and Safety of Acoziborole in Patients with Human African Trypanosomiasis Caused by Trypanosoma Brucei Gambiense: a Multicentre, Open-Label, Single-Arm, Phase 2\/3 Trial","author":"Kumeso","year":"2022"},{"key":"10.1016\/j.ejmech.2023.115176_bib11","first-page":"658","article-title":"FDA Approves First All-Oral Sleeping Sickness Drug","volume":"20","author":"Mullard","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2023.115176_bib12","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S1473-3099(13)70191-9","article-title":"Do we need new drugs against human African trypanosomiasis?","volume":"13","author":"Stich","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ejmech.2023.115176_bib13","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.pt.2012.12.005","article-title":"Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story","volume":"29","author":"Baker","year":"2013","journal-title":"Trends Parasitol."},{"key":"10.1016\/j.ejmech.2023.115176_bib14","doi-asserted-by":"crossref","first-page":"966","DOI":"10.3201\/eid1406.071266","article-title":"High failure rates of melarsoprol for sleeping sickness, Democratic Republic of Congo","volume":"14","author":"Robays","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"10.1016\/j.ejmech.2023.115176_bib15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41579-022-00777-y","article-title":"Anti-trypanosomatid drug discovery: progress and challenges","volume":"21","author":"De Rycker","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ejmech.2023.115176_bib16","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1021\/jm101439s","article-title":"Synthesis and structure\u2013activity relationships of new quinolone-type molecules against Trypanosoma brucei","volume":"55","author":"Hiltensperger","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib17","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ejmech.2018.04.055","article-title":"Fluorine walk: the impact of fluorine in quinolone amides on their activity against African sleeping sickness","volume":"152","author":"Berninger","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib18","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1128\/AAC.01757-15","article-title":"Quinolone amides as antitrypanosomal lead compounds with in vivo activity","volume":"60","author":"Hiltensperger","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115176_bib19","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00436-004-1223-4","article-title":"The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure","volume":"94","author":"Cavalcanti","year":"2004","journal-title":"Parasitol. Res."},{"key":"10.1016\/j.ejmech.2023.115176_bib20","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a025320","article-title":"Topoisomerase inhibitors: fluoroquinolone mechanisms of action and resistance","volume":"6","author":"Hooper","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.ejmech.2023.115176_bib21","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1021\/acs.jmedchem.8b01365","article-title":"Improvement of aqueous solubility of lapatinib-derived analogues: identification of a quinolinimine lead for human African trypanosomiasis drug development","volume":"62","author":"Bachovchin","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib22","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nature22308","article-title":"Predictive compound accumulation rules yield a broad-spectrum antibiotic","volume":"545","author":"Richter","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2023.115176_bib23","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.pt.2018.04.002","article-title":"Melarsoprol resistance in African trypanosomiasis","volume":"34","author":"Fairlamb","year":"2018","journal-title":"Trends Parasitol."},{"key":"10.1016\/j.ejmech.2023.115176_bib24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/BC20040095","article-title":"Aquaporins from pathogenic protozoan parasites: structure, function and potential for chemotherapy","volume":"97","author":"Beitz","year":"2005","journal-title":"Biol. Cell."},{"key":"10.1016\/j.ejmech.2023.115176_bib25","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ejmech.2016.07.001","article-title":"Design, synthesis and biological evaluation of novel azaspiro analogs of linezolid as antibacterial and antitubercular agents","volume":"122","author":"Gadekar","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib26","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1021\/ja01265a088","article-title":"The synthesis of certain substituted quinolines and 5,6-benzoquinolines","volume":"61","author":"Gould","year":"1939","journal-title":"J. Amer. Chem. Soc."},{"key":"10.1016\/j.ejmech.2023.115176_bib27","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/recl.19660851206","article-title":"Electrophilic chlorination by sulfuryl chloride","volume":"85","author":"Bolton","year":"1966","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"10.1016\/j.ejmech.2023.115176_bib28","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1055\/s-0032-1317795","article-title":"Tribromoisocyanuric acid in trifluoroacetic acid: an efficient system for smooth brominating of moderately deactivated Arenes","volume":"24","author":"Esteves","year":"2013","journal-title":"Synlett"},{"issue":"1987","key":"10.1016\/j.ejmech.2023.115176_bib29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jlac.198719870106","article-title":"Cycloaracylierung von Enaminen, I. Synthese von 4\u2010Chinolon\u20103\u2010carbons\u00e4uren","author":"Grohe","year":"1987","journal-title":"Liebigs Ann. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib30","doi-asserted-by":"crossref","first-page":"7133","DOI":"10.1021\/jo034710+","article-title":"A direct synthesis of 1-Aryl- and 1-Alkenylcyclopropylamines from Aryl and Alkenyl nitriles","volume":"68","author":"Bertus","year":"2003","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib31","doi-asserted-by":"crossref","first-page":"5900","DOI":"10.1021\/acs.jmedchem.5b00511","article-title":"Synthesis and in vitro Anticancer activity of the first class of dual inhibitors of REV-ERB\u03b2 and Autophagy","volume":"58","author":"Torrente","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib32","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1016\/j.bmcl.2008.09.042","article-title":"(3R)-3-Amino-4-(2,4,5-trifluorophenyl)-N-{4-[6-(2-methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide as a potent dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes","volume":"18","author":"Nitta","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2023.115176_bib33","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1021\/ja01234a009","article-title":"Hydrogenation of basic nitriles with Raney nickel","volume":"66","author":"Huber","year":"1944","journal-title":"J. Amer. Chem. Soc."},{"key":"10.1016\/j.ejmech.2023.115176_bib34","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1246\/bcsj.76.1257","article-title":"Convenient synthesis of 4-Hydroxy-1, 2-dihydroquinoline-3-carboxylate derivatives and 4-oxo-1, 2, 3, 4-tetrahydroquinoline-3-carboxylates","volume":"76","author":"Kobayashi","year":"2003","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"10.1016\/j.ejmech.2023.115176_bib35","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1016\/S0040-4039(01)83457-2","article-title":"A mild, general method for conversion of esters to amides","volume":"18","author":"Basha","year":"1977","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2023.115176_bib36","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s10822-011-9478-1","article-title":"Qualitative prediction of blood\u2013brain barrier permeability on a large and refined dataset","volume":"25","author":"Muehlbacher","year":"2011","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2023.115176_bib37","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/jps.2600760902","article-title":"Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design","volume":"76","author":"Hansch","year":"1987","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2023.115176_bib38","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1021\/mp0700209","article-title":"The rule of five revisited: Applying log D in place of log P in drug-likeness filters","volume":"4","author":"Bhal","year":"2007","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.ejmech.2023.115176_bib39","series-title":"Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug Metabolism for Industrial Scientists","first-page":"44","article-title":"4.2.4. Partition and distribution coefficients","author":"Kwon","year":"2001"},{"key":"10.1016\/j.ejmech.2023.115176_bib40","doi-asserted-by":"crossref","DOI":"10.1038\/nrd.2018.197","article-title":"Re-assessing the rule of 5, two decades on","volume":"17","author":"Mullard","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2023.115176_bib41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.addr.2016.05.007","article-title":"BDDCS, the Rule of 5 and drugability","volume":"101","author":"Benet","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejmech.2023.115176_bib42","series-title":"OECD Guidelines for the Testing of Chemicals","article-title":"117: partition coefficient (n-octanol\/water), HPLC method","author":"No","year":"2022"},{"key":"10.1016\/j.ejmech.2023.115176_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.molstruc.2020.129122","article-title":"Synthesis and characterization of anilinium ionic liquids: exploring effect of \u03c0-\u03c0 ring stacking","volume":"1225","author":"Baker","year":"2021","journal-title":"J. Mol. Struct."},{"key":"10.1016\/j.ejmech.2023.115176_bib44","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/cbic.200301023","article-title":"Fluorine in medicinal Chemistry","volume":"5","author":"B\u00f6hm","year":"2004","journal-title":"Chembiochem"},{"key":"10.1016\/j.ejmech.2023.115176_bib45","series-title":"4-Chinolon-3-carboxamide: Entwicklung neuer Wirkstoffe zur Behandlung der afrikanischen Schlafkrankheit","author":"Hiltensperger","year":"2013"},{"key":"10.1016\/j.ejmech.2023.115176_bib46","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.2174\/138955707782331722","article-title":"Privileged structures: a useful concept for the rational design of new lead drug candidates","volume":"7","author":"Duarte","year":"2007","journal-title":"Mini Rev. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115176_bib47","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1517\/17460441.2011.550914","article-title":"The concept of privileged structures in rational drug design: focus on acridine and quinoline scaffolds in neurodegenerative and protozoan diseases","volume":"6","author":"Bongarzone","year":"2011","journal-title":"Expert Opin. Drug Discov."},{"key":"10.1016\/j.ejmech.2023.115176_bib48","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1021\/om100106e","article-title":"NMR chemical shifts of trace impurities: common laboratory solvents, organics, and gases in deuterated solvents relevant to the organometallic chemist","volume":"29","author":"Fulmer","year":"2010","journal-title":"Organometallics"},{"key":"10.1016\/j.ejmech.2023.115176_bib49","doi-asserted-by":"crossref","first-page":"985","DOI":"10.2307\/3282883","article-title":"Continuous cultivation of trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers","volume":"75","author":"Hirumi","year":"1989","journal-title":"J. Parasitol. Res."},{"key":"10.1016\/j.ejmech.2023.115176_bib50","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0001-706X(97)00079-X","article-title":"The Alamar Blue\u00ae assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro","volume":"68","author":"R\u00e4z","year":"1997","journal-title":"Acta Trop."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423000910?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423000910?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:51:03Z","timestamp":1759330263000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423000910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":49,"alternative-id":["S0223523423000910"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115176","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis and biological evaluations of quinolone amides against African trypanosomiasis with improved solubility","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115176","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115176"}}