{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T12:42:30Z","timestamp":1782736950945,"version":"3.54.5"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["8167335"],"award-info":[{"award-number":["8167335"]}]},{"name":"National Natural Science Foundation of China","award":["21878022"],"award-info":[{"award-number":["21878022"]}]},{"DOI":"10.13039\/501100005085","name":"Beijing Institute of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005085","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":[[2019,5]]},"DOI":"10.1016\/j.ejmech.2019.02.073","type":"journal-article","created":{"date-parts":[[2019,3,3]],"date-time":"2019-03-03T09:24:20Z","timestamp":1551605060000},"page":"1-20","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["Design, synthesis and structure-activity relationships of novel macrolones: Hybrids of 2-fluoro 9-oxime ketolides and carbamoyl quinolones with highly improved activity against resistant pathogens"],"prefix":"10.1016","volume":"169","author":[{"given":"Cong-Xuan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Zhi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan-Sheng","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Chao","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cushman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Hua","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2019.02.073_bib1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrmicro3155","article-title":"Ribosome-targeting antibiotics and mechanisms of bacterial resistance","volume":"12","author":"Wilson","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ejmech.2019.02.073_bib2","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/35101544","article-title":"Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria","volume":"413","author":"Schlunzen","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2019.02.073_bib3","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1128\/AAC.05658-11","article-title":"Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in asian countries: an asian network for surveillance of resistant pathogens (ANSORP) study","volume":"56","author":"Kim","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2019.02.073_bib4","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01230-17","article-title":"In\u00a0vitro activity of the novel lactone ketolide nafithromycin (WCK 4873) against contemporary clinical bacteria from a global surveillance program","volume":"61","author":"Flamm","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2019.02.073_bib5","doi-asserted-by":"crossref","first-page":"4080","DOI":"10.1021\/jm980240d","article-title":"Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives): a new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens","volume":"41","author":"Agouridas","year":"1998","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib6","doi-asserted-by":"crossref","first-page":"664","DOI":"10.7164\/antibiotics.54.664","article-title":"Synthesis and antibacterial activity of the tricyclic ketolides TE-802 and its analogs","volume":"54","author":"Kashimura","year":"2001","journal-title":"J.\u00a0Antibiot."},{"key":"10.1016\/j.ejmech.2019.02.073_bib7","doi-asserted-by":"crossref","first-page":"17152","DOI":"10.1073\/pnas.1007988107","article-title":"Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action","volume":"107","author":"Dunkle","year":"2010","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ejmech.2019.02.073_bib8","doi-asserted-by":"crossref","first-page":"17158","DOI":"10.1073\/pnas.1008685107","article-title":"Revisiting the structures of several antibiotics bound to the bacterial ribosome","volume":"107","author":"Bulkley","year":"2010","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ejmech.2019.02.073_bib9","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1016\/S0960-894X(99)00534-X","article-title":"Synthesis and antibacterial activity of HMR 3647 a new ketolide highly potent against erythromycin-resistant and susceptible pathogens","volume":"9","author":"Denis","year":"1999","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.02.073_bib10","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.2174\/15680266113136660223","article-title":"Structure-activity relationships and mechanism of action of macrolides derived from erythromycin as antibacterial agents","volume":"13","author":"Liang","year":"2013","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib11","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.1021\/jm900729s","article-title":"Discovery of azetidinyl ketolides for the treatment of susceptible and multidrug resistant community-acquired respiratory tract infections","volume":"52","author":"Magee","year":"2009","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib12","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1517\/13543784.2014.954036","article-title":"The wobbly status of ketolides: where do we stand?","volume":"23","author":"Georgopapadakou","year":"2014","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.ejmech.2019.02.073_bib13","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1517\/13543776.2010.505921","article-title":"New macrolide, lincosaminide and streptogramin B antibiotics","volume":"20","author":"Kirst","year":"2010","journal-title":"Expert Opin. Ther. Pat."},{"key":"10.1016\/j.ejmech.2019.02.073_bib14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/ja.2016.137","article-title":"Nature nurtures the design of new semi-synthetic macrolide antibiotics","volume":"70","author":"Fernandes","year":"2017","journal-title":"J.\u00a0Antibiot."},{"key":"10.1016\/j.ejmech.2019.02.073_bib15","doi-asserted-by":"crossref","first-page":"6420","DOI":"10.1016\/j.bmc.2016.08.035","article-title":"The solithromycin journey-It is all in the chemistry","volume":"24","author":"Fernandes","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib16","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1111\/bph.13936","article-title":"The macrolide antibiotic renaissance","volume":"174","author":"Dinos","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2019.02.073_bib17","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nature17967","article-title":"A\u00a0platform for the discovery of new macrolide antibiotics","volume":"533","author":"Seiple","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2019.02.073_bib18","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1021\/jm0102349","article-title":"Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug-resistant respiratory pathogens","volume":"44","author":"Ma","year":"2001","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib19","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1128\/AAC.01469-10","article-title":"In\u00a0vitro antibacterial activity of modithromycin, a novel 6,11-bridged bicyclolide, against respiratory pathogens, including macrolide-resistant gram-positive cocci","volume":"55","author":"Sato","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2019.02.073_bib20","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0969-2126(03)00022-4","article-title":"Structural basis for the antibiotic activity of ketolides and azalides","volume":"11","author":"Schlunzen","year":"2003","journal-title":"Structure"},{"key":"10.1016\/j.ejmech.2019.02.073_bib21","doi-asserted-by":"crossref","first-page":"6054","DOI":"10.1016\/j.bmc.2005.06.003","article-title":"9-Oxime-3-ketolides: modification at the C-11,12-diol moiety and antibacterial activities against key respiratory pathogens","volume":"13","author":"Nomura","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib22","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1016\/j.ejmech.2010.05.008","article-title":"Synthesis and antibacterial activities of 6-O-methylerythromycin A 9-O-(3-aryl-2-propenyl) oxime ketolide, 2,3-enol ether, and alkylide analogues","volume":"45","author":"Liang","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib23","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejmech.2012.10.054","article-title":"Synthesis, antibacterial activity and docking of 14-membered 9-O-(3-arylalkyl) oxime 11,12-cyclic carbonate ketolides","volume":"59","author":"Liang","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib24","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tibs.2018.06.011","article-title":"How macrolide antibiotics work","volume":"43","author":"Vazquez-Laslop","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.ejmech.2019.02.073_bib25","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.cell.2012.09.018","article-title":"Selective protein synthesis by ribosomes with a drug-obstructed exit tunnel","volume":"151","author":"Kannan","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2019.02.073_bib26","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.ejmech.2017.11.082","article-title":"4-Quinolone derivatives and their activities against Gram positive pathogens","volume":"143","author":"Zhang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib27","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.201800141","article-title":"Recent updates of fluoroquinolones as antibacterial agents","volume":"351","author":"Ezelarab","year":"2018","journal-title":"Arch. Pharm."},{"key":"10.1016\/j.ejmech.2019.02.073_bib28","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1016\/S0960-894X(00)00392-9","article-title":"beta-keto-ester chemistry and ketolides. Synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides","volume":"10","author":"Denis","year":"2000","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.02.073_bib29","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1128\/AAC.00860-10","article-title":"Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis","volume":"54","author":"Llano-Sotelo","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2019.02.073_bib30","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/ja.2009.89","article-title":"Design, synthesis and antibacterial activity of a novel alkylide: 3-O-(3-aryl-propenyl)clarithromycin derivatives","volume":"62","author":"Liang","year":"2009","journal-title":"J.\u00a0Antibiot."},{"key":"10.1016\/j.ejmech.2019.02.073_bib31","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.bmcl.2012.12.070","article-title":"Synthesis and antibacterial activity of 9-oxime ether non-ketolides, and novel binding mode of alkylides with bacterial rRNA","volume":"23","author":"Liang","year":"2013","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.02.073_bib32","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1016\/j.bmc.2015.08.020","article-title":"Synthesis and structure-activity relationships of novel 9-oxime acylides with improved bactericidal activity","volume":"23","author":"Han","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib33","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.bmcl.2017.02.041","article-title":"Design, synthesis and structure -bactericidal activity relationships of novel 9-oxime ketolides and reductive epimers of acylides","volume":"27","author":"Tian","year":"2017","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.02.073_bib34","series-title":"Comprehensive Medicinal Chemistry II","first-page":"519","article-title":"7.18 macrolide antibiotics","author":"Kaneko","year":"2007"},{"key":"10.1016\/j.ejmech.2019.02.073_bib35","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1016\/j.ejmech.2011.05.002","article-title":"Synthesis, activity and pharmacokinetics of novel antibacterial 15-membered ring macrolones","volume":"46","author":"Fajdetic","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib36","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1021\/ml100253p","article-title":"Discovery of 4 ''-ether linked azithromycin-quinolone hybrid series: influence of the central linker on the antibacterial activity","volume":"2","author":"Pavlovic","year":"2011","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2019.02.073_bib37","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2174\/1568026616666160927160036","article-title":"Macrolide hybrid compounds: drug discovery opportunities in AntiInfective and anti-inflammatory area","volume":"17","author":"Paljetak","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib38","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1016\/j.bmcl.2010.04.062","article-title":"Novel 8a-aza-8a-homoerythromycin-4 ''-(3-substituted-amino)propionates with broad spectrum antibacterial activity","volume":"20","author":"Hutinec","year":"2010","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.02.073_bib39","doi-asserted-by":"crossref","first-page":"8566","DOI":"10.1016\/j.bmc.2010.10.024","article-title":"Novel hybrids of 15-membered 8a- and 9a-azahomoerythromycin A ketolides and quinolones as potent antibacterials","volume":"18","author":"Pavlovic","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib40","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejmech.2016.09.022","article-title":"Synthesis of novel 15-membered 8a-azahomoerythromycin A acylides: consequences of structural modification at the C-3 and C-6 position on antibacterial activity","volume":"125","author":"Pavlovic","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.02.073_bib41","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1021\/ol006226o","article-title":"Synthesis of 2-fluoro-6-O-propargyl-11,12-carbamate ketolides. A novel class of antibiotics","volume":"2","author":"Phan","year":"2000","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2019.02.073_bib42","series-title":"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Eighth Edition M07-A8","author":"Clinical and Laboratory Standards Institute","year":"2009"},{"key":"10.1016\/j.ejmech.2019.02.073_bib43","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2174\/1568026013395001","article-title":"Metabolism profiling, and cytochrome P450 inhibition & induction in drug discovery","volume":"1","author":"Yan","year":"2001","journal-title":"Curr. Top. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523419302053?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523419302053?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T10:40:21Z","timestamp":1565174421000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523419302053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":43,"alternative-id":["S0223523419302053"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2019.02.073","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis and structure-activity relationships of novel macrolones: Hybrids of 2-fluoro 9-oxime ketolides and carbamoyl quinolones with highly improved activity against resistant pathogens","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2019.02.073","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}