{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:27:36Z","timestamp":1775237256832,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T00:00:00Z","timestamp":1548633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473098"],"award-info":[{"award-number":["81473098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473099"],"award-info":[{"award-number":["81473099"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703366"],"award-info":[{"award-number":["81703366"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti\u2010influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound <jats:bold>6092B\u2010E5<\/jats:bold> has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti\u2010IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds <jats:bold>D<jats:sub>1<\/jats:sub><\/jats:bold>, <jats:bold>D<jats:sub>3<\/jats:sub><\/jats:bold>, <jats:bold>D<jats:sub>9<\/jats:sub><\/jats:bold>, <jats:bold>G<jats:sub>1<\/jats:sub><\/jats:bold>, <jats:bold>G<jats:sub>3<\/jats:sub><\/jats:bold>, <jats:bold>G<jats:sub>12<\/jats:sub><\/jats:bold> and <jats:bold>G<jats:sub>23<\/jats:sub><\/jats:bold> were identified as promising anti\u2010IAV candidates with excellent anti\u2010IAV efficacy (IC<jats:sub>50<\/jats:sub> values of 3.06\u20135.77\u2005\u03bc<jats:sc>m<\/jats:sc>) and low cytotoxicity (CC<jats:sub>50<\/jats:sub> values up to and beyond 100\u2005\u03bc<jats:sc>m<\/jats:sc>). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization.<\/jats:p>","DOI":"10.1002\/cbdv.201800577","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T03:15:34Z","timestamp":1544411734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and Biological Evaluation of Substituted Indole and Its Analogs as Influenza A Virus Inhibitors"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8544-8442","authenticated-orcid":false,"given":"Xuandi","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy Jinzhou Medical University  Jinzhou 121001 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo\u2010Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College  Beijing 100050 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujia","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College  Beijing 100050 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College  Beijing 100050 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juxian","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College  Beijing 100050 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziqiang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jinzhou Medical University  Jinzhou 121001 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jinzhou Medical University  Jinzhou 121001 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Cen","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College  Beijing 100050 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yucheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College  Beijing 100050 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,28]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"crossref","unstructured":"A. Stevaert L. Naesens \u2018The Influenza Virus Polymerase Complex: An Update on Its Structure Functions and Significance for Antiviral Drug Design\u2019 Med. Res. Rev.2016 36 1127\u20131173.","DOI":"10.1002\/med.21401"},{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","unstructured":"A.\u2005D. Iuliano K.\u2005M. Roguski H.\u2005H. Chang D.\u2005J. Muscatello R. Palekar S. Tempia C. Cohen J.\u2005M. Gran D. Schanzer B.\u2005J. Cowling P. Wu J. Kyncl L.\u2005W. Ang M. Park M. Redlberger-Fritz H. Yu L. Espenhain A. Krishnan G. Emukule L. van Asten S. Pereira\u2005da\u2005Silva S. Aungkulanon U. Buchholz M.-A. Widdowson J.\u2005S. Bresee \u2018Estimates of global seasonal influenza-associated respiratory mortality: a modelling study\u2019 Lancet2017 391 1285\u20131300.","DOI":"10.1016\/S0140-6736(17)33293-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","unstructured":"L. Simonsen P. Spreeuwenberg R. Lustig R.\u2005J. Taylor D.\u2005M. Fleming M. Kroneman M.\u2005D. Van\u2005Kerkhove A.\u2005W. Mounts W.\u2005J. Paget \u2018Global mortality estimates for the 2009 influenza pandemic from the GLaMOR project: a modeling study\u2019 PLoS Med.2013 10 e1001558.","DOI":"10.1371\/journal.pmed.1001558"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","unstructured":"J.\u2005M. Gran O. Kacelnik A.\u2005M. Grjibovski P. Aavitsland B.\u2005G. Iversen \u2018Counting pandemic deaths: comparing reported numbers of deaths from influenza A(H1\u2005N1)pdm09 with estimated excess mortality\u2019 Influenza Other Respir. Viruses2013 7 1370\u20131379.","DOI":"10.1111\/irv.12125"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","unstructured":"M. Lemaitre F. Carrat G. Rey M. Miller L. Simonsen C. Viboud \u2018Mortality burden of the 2009A\/H1N1 influenza pandemic in France: comparison to seasonal influenza and the A\/H3N2 pandemic\u2019 PLoS One2012 7 e45051.","DOI":"10.1371\/journal.pone.0045051"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","unstructured":"T. L\u00f3pez-Cuadrado S. de Mateo S. Jim\u00e9nez-Jorge C. Savulescu A. Larrauri \u2018Influenza-related mortality in Spain 1999\u20132005\u2019 Gac. Sanit.2012 26 325\u2013329.","DOI":"10.1016\/j.gaceta.2011.09.033"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","unstructured":"D.\u2005J. Muscatello A.\u2005T. Newall D.\u2005E. Dwyer C.\u2005R. Macintyre \u2018Mortality attributable to seasonal and pandemic influenza Australia 2003 to 2009 using a novel time series smoothing approach\u2019 PLoS One2014 8 e64734.","DOI":"10.1371\/journal.pone.0064734"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","unstructured":"M. Redlberger-Fritz J.\u2005H. Aberle T. Popow-Kraupp M. Kundi \u2018Attributable deaths due to influenza: a comparative study of seasonal and pandemic influenza\u2019 Eur. J. Epidemiol.2012 27 567\u201375.","DOI":"10.1007\/s10654-012-9701-y"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","unstructured":"C.\u2005C. Wijngaard L. Asten M.\u2005P. Koopmans W. van\u2005Pelt N.\u2005J. Nagelkerke C.\u2005C. Wielders A. van\u2005Lier W. van\u2005der\u2005Hoek A. Meijer G.\u2005A. Donker F. Dijkstra C. Harmsen M.\u2005A. van\u2005der\u2005Sande M. Kretzschmar \u2018Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children\u2019 PLoS One2012 7 e31197.","DOI":"10.1371\/journal.pone.0031197"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","unstructured":"M. Park P. Wu E. Goldstein W.\u2005J. Kim B.\u2005J. Cowling \u2018Influenza-Associated Excess Mortality in South Korea\u2019 Am. J. Prev. Med.2016 50 e111\u2013e119.","DOI":"10.1016\/j.amepre.2015.09.028"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","unstructured":"C. Cohen S. Walaza F.\u2005K. Treurnicht M. McMorrow S.\u2005A. Madhi J.\u2005M. McAnerney S. Tempia \u2018In- and Out-of-hospital Mortality Associated with Seasonal and Pandemic Influenza and Respiratory Syncytial Virus in South Africa 2009\u20132013\u2019 Clin. Infect. Dis.2018 66 95\u2013103.","DOI":"10.1093\/cid\/cix740"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","unstructured":"R.-X. Gu L.-A. Liu D.-Q. Wei \u2018Structural and energetic analysis of drug inhibition of the influenza A M2 proton channel\u2019 Trends Pharmacol. Sci.2013 34 571\u2013580.","DOI":"10.1016\/j.tips.2013.08.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","unstructured":"T. Jefferson V. Demicheli C. Di\u2005Pietranton D. Rivetti \u2018Amantadine and rimantadine for influenza A in adults\u2019 Cochrane Database Syst. Rev.2006 2 CD001169.","DOI":"10.1002\/14651858.CD001169.pub3"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","unstructured":"V.\u2005M. Deyde X. Xu R.\u2005A. Bright M. Shaw C.\u2005B. Smith Y. Zhang Y. Shu L.\u2005V. Gubareva N.\u2005J. Cox A.\u2005I. Klimov \u2018Surveillance of resistance to adamantanes among influenza A(H3\u2005N2) and A(H1\u2005N1) viruses isolated worldwide\u2019 J. Infect. Dis.2007 196 249\u2013257.","DOI":"10.1086\/518936"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","unstructured":"C. Paules K. Subbarao \u2018Influenza\u2019 Lancet2017 390 697\u2013708.","DOI":"10.1016\/S0140-6736(17)30129-0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","unstructured":"A. Moscona \u2018Global transmission of oseltamivir-resistant influenza\u2019 New Engl. J. Med.2009 360 953\u2013956.","DOI":"10.1056\/NEJMp0900648"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","unstructured":"J.\u2005L. McKimm-Breschkin A.\u2005M. Fry \u2018Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses\u2019 Antiviral Res.2016 129 21\u201338.","DOI":"10.1016\/j.antiviral.2016.01.012"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","unstructured":"J. Beigel M. Bray \u2018Current and future antiviral therapy of severe seasonal and avian influenza\u2019 Antiviral Res.2008 78 91\u2013102.","DOI":"10.1016\/j.antiviral.2008.01.003"},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","unstructured":"M.\u2005G. Ison \u2018Optimizing antiviral therapy for influenza: understanding the evidence\u2019 Expert Rev. Anti-Infect. Ther.2015 13 417\u2013425.","DOI":"10.1586\/14787210.2015.1018183"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","unstructured":"M.\u2005D. Reddy F.\u2005R. Fronczek E.\u2005B. Watkins \u2018Rh-catalyzed regioselective C\u2009\u2212H bond functionalization: access to quinoline-branched amines and dimers\u2019 Org. Lett.2016 18 5620\u20135623.","DOI":"10.1021\/acs.orglett.6b02848"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","unstructured":"D.\u2005R. Motati D. Uredi E.\u2005B. Watkins \u2018A general method for the metal-free regioselective remote C\u2212H halogenation of 8-substituted quinolines\u2019 Chem. Sci.2018 9 1782\u20131788.","DOI":"10.1039\/C7SC04107A"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","unstructured":"D. Uredi D.\u2005R. Motati E.\u2005B. Watkins \u2018A Unified Strategy for the Synthesis of \u03b2-Carbolines \u03b3-Carbolines and Other Fused Azaheteroaromatics under Mild Metal-Free Conditions\u2019 Org. Lett.2018 20 6336\u20136339.","DOI":"10.1021\/acs.orglett.8b02441"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","unstructured":"G. Raju R. Srinivas M.\u2005D. Reddy C.\u2005R. Reddy N. Nagesh \u2018Studies on non-covalent interaction of coumarin attached pyrimidine and 1-methyl indole 1 2 3-triazole analogues with intermolecular telomeric G-quadruplex DNA using ESI-MS and spectroscopy\u2019 Nucleosides Nucleotides Nucleic Acids2014 33 489\u2013506.","DOI":"10.1080\/15257770.2014.891742"},{"key":"e_1_2_7_24_1","doi-asserted-by":"crossref","unstructured":"Q. Gao Z. Wang Z. Liu X. Li Y. Zhang Z. Zhang S. Cen \u2018A cell-based high-throughput approach to identify inhibitors of influenza A virus\u2019 Acta Pharm. Sin. B2014 4 301\u2013306.","DOI":"10.1016\/j.apsb.2014.06.005"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcbdv.201800577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.201800577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.201800577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T11:17:49Z","timestamp":1694690269000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.201800577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,28]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/cbdv.201800577"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.201800577","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,28]]},"assertion":[{"value":"2018-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1800577"}}