Synthesis and biological evaluation of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives as potential MERS-CoV inhibitors
Identifieur interne : 000663 ( Pmc/Corpus ); précédent : 000662; suivant : 000664Synthesis and biological evaluation of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives as potential MERS-CoV inhibitors
Auteurs : Ji Hye Yoon ; Jun Young Lee ; Jihye Lee ; Young Sup Shin ; Sangeun Jeon ; Dong Eon Kim ; Jung Sun Min ; Jong Hwan Song ; Seungtaek Kim ; Sunoh Kwon ; Young-Hee Jin ; Min Seong Jang ; Hyoung Rae Kim ; Chul Min ParkSource :
- Bioorganic & Medicinal Chemistry Letters [ 0960-894X ] ; 2019.
Abstract
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DOI: 10.1016/j.bmcl.2019.126727
PubMed: 31624041
PubMed Central: 7126094
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis and biological evaluation of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one derivatives as potential MERS-CoV inhibitors</title><author><name sortKey="Yoon, Ji Hye" sort="Yoon, Ji Hye" uniqKey="Yoon J" first="Ji Hye" last="Yoon">Ji Hye Yoon</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Jun Young" sort="Lee, Jun Young" uniqKey="Lee J" first="Jun Young" last="Lee">Jun Young Lee</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Jihye" sort="Lee, Jihye" uniqKey="Lee J" first="Jihye" last="Lee">Jihye Lee</name><affiliation><nlm:aff id="af010">Respiratory Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</nlm:aff></affiliation></author><author><name sortKey="Shin, Young Sup" sort="Shin, Young Sup" uniqKey="Shin Y" first="Young Sup" last="Shin">Young Sup Shin</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Jeon, Sangeun" sort="Jeon, Sangeun" uniqKey="Jeon S" first="Sangeun" last="Jeon">Sangeun Jeon</name><affiliation><nlm:aff id="af010">Respiratory Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Dong Eon" sort="Kim, Dong Eon" uniqKey="Kim D" first="Dong Eon" last="Kim">Dong Eon Kim</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Min, Jung Sun" sort="Min, Jung Sun" uniqKey="Min J" first="Jung Sun" last="Min">Jung Sun Min</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Song, Jong Hwan" sort="Song, Jong Hwan" uniqKey="Song J" first="Jong Hwan" last="Song">Jong Hwan Song</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Seungtaek" sort="Kim, Seungtaek" uniqKey="Kim S" first="Seungtaek" last="Kim">Seungtaek Kim</name><affiliation><nlm:aff id="af020">Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kwon, Sunoh" sort="Kwon, Sunoh" uniqKey="Kwon S" first="Sunoh" last="Kwon">Sunoh Kwon</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Jin, Young Hee" sort="Jin, Young Hee" uniqKey="Jin Y" first="Young-Hee" last="Jin">Young-Hee Jin</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Jang, Min Seong" sort="Jang, Min Seong" uniqKey="Jang M" first="Min Seong" last="Jang">Min Seong Jang</name><affiliation><nlm:aff id="af025">Department of Non-Clinical Studies, Korea Institute of Toxicology, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Hyoung Rae" sort="Kim, Hyoung Rae" uniqKey="Kim H" first="Hyoung Rae" last="Kim">Hyoung Rae Kim</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Park, Chul Min" sort="Park, Chul Min" uniqKey="Park C" first="Chul Min" last="Park">Chul Min Park</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31624041</idno><idno type="pmc">7126094</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126094</idno><idno type="RBID">PMC:7126094</idno><idno type="doi">10.1016/j.bmcl.2019.126727</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000663</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000663</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Synthesis and biological evaluation of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one derivatives as potential MERS-CoV inhibitors</title><author><name sortKey="Yoon, Ji Hye" sort="Yoon, Ji Hye" uniqKey="Yoon J" first="Ji Hye" last="Yoon">Ji Hye Yoon</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Jun Young" sort="Lee, Jun Young" uniqKey="Lee J" first="Jun Young" last="Lee">Jun Young Lee</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Jihye" sort="Lee, Jihye" uniqKey="Lee J" first="Jihye" last="Lee">Jihye Lee</name><affiliation><nlm:aff id="af010">Respiratory Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</nlm:aff></affiliation></author><author><name sortKey="Shin, Young Sup" sort="Shin, Young Sup" uniqKey="Shin Y" first="Young Sup" last="Shin">Young Sup Shin</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Jeon, Sangeun" sort="Jeon, Sangeun" uniqKey="Jeon S" first="Sangeun" last="Jeon">Sangeun Jeon</name><affiliation><nlm:aff id="af010">Respiratory Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Dong Eon" sort="Kim, Dong Eon" uniqKey="Kim D" first="Dong Eon" last="Kim">Dong Eon Kim</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Min, Jung Sun" sort="Min, Jung Sun" uniqKey="Min J" first="Jung Sun" last="Min">Jung Sun Min</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Song, Jong Hwan" sort="Song, Jong Hwan" uniqKey="Song J" first="Jong Hwan" last="Song">Jong Hwan Song</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Seungtaek" sort="Kim, Seungtaek" uniqKey="Kim S" first="Seungtaek" last="Kim">Seungtaek Kim</name><affiliation><nlm:aff id="af020">Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kwon, Sunoh" sort="Kwon, Sunoh" uniqKey="Kwon S" first="Sunoh" last="Kwon">Sunoh Kwon</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Jin, Young Hee" sort="Jin, Young Hee" uniqKey="Jin Y" first="Young-Hee" last="Jin">Young-Hee Jin</name><affiliation><nlm:aff id="af015">Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</nlm:aff></affiliation></author><author><name sortKey="Jang, Min Seong" sort="Jang, Min Seong" uniqKey="Jang M" first="Min Seong" last="Jang">Min Seong Jang</name><affiliation><nlm:aff id="af025">Department of Non-Clinical Studies, Korea Institute of Toxicology, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Hyoung Rae" sort="Kim, Hyoung Rae" uniqKey="Kim H" first="Hyoung Rae" last="Kim">Hyoung Rae Kim</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author><author><name sortKey="Park, Chul Min" sort="Park, Chul Min" uniqKey="Park C" first="Chul Min" last="Park">Chul Min Park</name><affiliation><nlm:aff id="af005">Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</nlm:aff></affiliation></author></analytic><series><title level="j">Bioorganic & Medicinal Chemistry Letters</title><idno type="ISSN">0960-894X</idno><idno type="eISSN">1464-3405</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Graphical abstract</title><fig id="f0020" position="anchor"><graphic xlink:href="ga1_lrg"></graphic></fig></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cotten, M" uniqKey="Cotten M">M. Cotten</name></author><author><name sortKey="Watson, S J" uniqKey="Watson S">S.J. Watson</name></author><author><name sortKey="Zumla, A I" uniqKey="Zumla A">A.I. Zumla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liang, R" uniqKey="Liang R">R. Liang</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Zhang, N" uniqKey="Zhang N">N. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F W" uniqKey="Chan J">J.F.W. Chan</name></author><author><name sortKey="Lau, S K P" uniqKey="Lau S">S.K.P. Lau</name></author><author><name sortKey="To, K K W" uniqKey="To K">K.K.W. To</name></author><author><name sortKey="Cheng, V C C" uniqKey="Cheng V">V.C.C. Cheng</name></author><author><name sortKey="Woo, P C Y" uniqKey="Woo P">P.C.Y. Woo</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.-Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. De Wit</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N. van Doremalen</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="Munster, V J" uniqKey="Munster V">V.J. Munster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dyall, J" uniqKey="Dyall J">J. Dyall</name></author><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C.M. Coleman</name></author><author><name sortKey="Hart, B J" uniqKey="Hart B">B.J. Hart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wilde, A H" uniqKey="De Wilde A">A.H. de Wilde</name></author><author><name sortKey="Jochmans, D" uniqKey="Jochmans D">D. Jochmans</name></author><author><name sortKey="Posthuma, C C" uniqKey="Posthuma C">C.C. Posthuma</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kim, H J" uniqKey="Kim H">H.J. Kim</name></author><author><name sortKey="Kim, N" uniqKey="Kim N">N. Kim</name></author><author><name sortKey="Shum, D" uniqKey="Shum D">D. Shum</name></author><author><name sortKey="Huddar, S" uniqKey="Huddar S">S. Huddar</name></author><author><name sortKey="Park, C M" uniqKey="Park C">C.M. Park</name></author><author><name sortKey="Jang, S" uniqKey="Jang S">S. Jang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kang, D H" uniqKey="Kang D">D.-H. Kang</name></author><author><name sortKey="Jun, K Y" uniqKey="Jun K">K.-Y. Jun</name></author><author><name sortKey="Lee, J P" uniqKey="Lee J">J.P. Lee</name></author><author><name sortKey="Pak, C S" uniqKey="Pak C">C.S. Pak</name></author><author><name sortKey="Na, Y" uniqKey="Na Y">Y. Na</name></author><author><name sortKey="Kwon, Y" uniqKey="Kwon Y">Y. Kwon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, M C" uniqKey="Sharma M">M.C. Sharma</name></author><author><name sortKey="Sharma, S" uniqKey="Sharma S">S. Sharma</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Hwang, B H" uniqKey="Hwang B">B.H. Hwang</name></author><author><name sortKey="Park, S H" uniqKey="Park S">S.H. Park</name></author><author><name sortKey="Choi, E B" uniqKey="Choi E">E.B. Choi</name></author><author><name sortKey="Park, C S" uniqKey="Park C">C.S. Park</name></author><author><name sortKey="Lee, H K" uniqKey="Lee H">H.K. Lee</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="brief-report"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Bioorg Med Chem Lett</journal-id><journal-id journal-id-type="iso-abbrev">Bioorg. Med. Chem. Lett</journal-id><journal-title-group><journal-title>Bioorganic & Medicinal Chemistry Letters</journal-title></journal-title-group><issn pub-type="ppub">0960-894X</issn><issn pub-type="epub">1464-3405</issn><publisher><publisher-name>Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31624041</article-id><article-id pub-id-type="pmc">7126094</article-id><article-id pub-id-type="publisher-id">S0960-894X(19)30685-7</article-id><article-id pub-id-type="doi">10.1016/j.bmcl.2019.126727</article-id><article-id pub-id-type="publisher-id">126727</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Synthesis and biological evaluation of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one derivatives as potential MERS-CoV inhibitors</article-title></title-group><contrib-group><contrib contrib-type="author" id="au005"><name><surname>Yoon</surname><given-names>Ji Hye</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au010"><name><surname>Lee</surname><given-names>Jun Young</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au015"><name><surname>Lee</surname><given-names>Jihye</given-names></name><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au020"><name><surname>Shin</surname><given-names>Young Sup</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au025"><name><surname>Jeon</surname><given-names>Sangeun</given-names></name><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au030"><name><surname>Kim</surname><given-names>Dong Eon</given-names></name><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au035"><name><surname>Min</surname><given-names>Jung Sun</given-names></name><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au040"><name><surname>Song</surname><given-names>Jong Hwan</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au045"><name><surname>Kim</surname><given-names>Seungtaek</given-names></name><xref rid="af020" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au050"><name><surname>Kwon</surname><given-names>Sunoh</given-names></name><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au055"><name><surname>Jin</surname><given-names>Young-hee</given-names></name><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au060"><name><surname>Jang</surname><given-names>Min Seong</given-names></name><xref rid="af025" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au065"><name><surname>Kim</surname><given-names>Hyoung Rae</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au070"><name><surname>Park</surname><given-names>Chul Min</given-names></name><xref rid="af005" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="af005"><label>a</label>Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea</aff><aff id="af010"><label>b</label>Respiratory Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</aff><aff id="af015"><label>c</label>Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea</aff><aff id="af020"><label>d</label>Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea</aff><aff id="af025"><label>e</label>Department of Non-Clinical Studies, Korea Institute of Toxicology, Yuseong-gu, Daejeon 34114, South Korea</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding author.</corresp></author-notes><pub-date pub-type="pmc-release"><day>9</day><month>10</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>1</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>9</day><month>10</month><year>2019</year></pub-date><volume>29</volume><issue>23</issue><fpage>126727</fpage><lpage>126727</lpage><history><date date-type="received"><day>24</day><month>6</month><year>2019</year></date><date date-type="rev-recd"><day>6</day><month>9</month><year>2019</year></date><date date-type="accepted"><day>30</day><month>9</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Elsevier Ltd</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract abstract-type="graphical" id="ab005"><title>Graphical abstract</title><fig id="f0020" position="anchor"><graphic xlink:href="ga1_lrg"></graphic></fig></abstract><abstract id="ab010"><p>3-Acyl-2-phenylamino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one derivatives were synthesized and evaluated to show high anti-MERS-CoV inhibitory activities. Among them, 6,8-difluoro-3-isobutyryl-2-((2,3,4-trifluorophenyl)amino)quinolin-4(1<italic>H</italic>)-one (<bold>6u</bold>) exhibits high inhibitory effect (IC<sub>50</sub> = 86 nM) and low toxicity (CC<sub>50</sub> > 25 μM). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good <italic>in vivo</italic> PK properties.</p></abstract><kwd-group id="kg005"><title>Keywords</title><kwd>MERS-CoV</kwd><kwd>RNA virus</kwd><kwd>3-Acyl-2-amino-1,4-dihydroquinolin-4(1<italic>H</italic>)-ones</kwd><kwd>Inhibitor</kwd><kwd>SAR optimization</kwd></kwd-group></article-meta></front><body><p id="p0005">Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging, fatal virus that causes severe respiratory symptoms in humans with high mortality (about 38%), such as high fever, cough, shortness of breath, and acute pneumoniae.<xref rid="b0005" ref-type="bibr">1</xref>, <xref rid="b0010" ref-type="bibr">2</xref> MERS-CoV is a zoonotic coronavirus that can spread non-sustained person-to-person transmission.<xref rid="b0015" ref-type="bibr"><sup>3</sup></xref> Travel-related MERS-CoV infections continued to spread from the Arabian Peninsula to several other countries and caused epidemics with high fatal rates.<xref rid="b0020" ref-type="bibr"><sup>4</sup></xref></p><p id="p0010">MERS-CoV is a single-stranded, positive-sense RNA virus and uses host cellular components to accomplish various physiological processes, including internalization of the virion, genome replication, packaging and budding of the virions. Therefore, each stage of these steps of the virus life cycle can be targets for therapeutic inhibition. Screening of FDA-approved drugs for MERS-CoV identified many drugs with antiviral effects.<xref rid="b0025" ref-type="bibr">5</xref>, <xref rid="b0030" ref-type="bibr">6</xref> These drugs can be categorized into inhibitors disrupting endocytosis, interrupting MERS-CoV RNA replication and translation, and inhibitors with undefined mechanisms. To date, there are still no approved antiviral drugs.<xref rid="b0010" ref-type="bibr"><sup>2</sup></xref> Therefore, the development of therapeutics against MERS has received more and more attention.</p><p id="p0015">We began our investigation by screening 200,000 compounds of Korean Chemical Bank (KCB) against MERS-CoV using high content screening (HCS) platform of Institut Pasteur Korea (IPK).<xref rid="b0035" ref-type="bibr"><sup>7</sup></xref> Through this effort, 3-acetyl-6-chloro-2-(isopropylamino)-8-(trifluoromethyl)quinolin-4(1<italic>H</italic>)-one <bold>1</bold> was identified as a primary hit (<xref rid="f0005" ref-type="fig">Fig. 1</xref>). 1,4-Dihydroquinolin-4-one derivatives showed a broad range of pharmacological activities, such as antibacterial,<xref rid="b0040" ref-type="bibr"><sup>8</sup></xref> anti-neurodegenerative,<xref rid="b0045" ref-type="bibr"><sup>9</sup></xref> and anti-infammatory.<xref rid="b0050" ref-type="bibr"><sup>10</sup></xref> Here we report on the synthesis and biological effects of 3-acyl-2-amino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one derivatives.<fig id="f0005"><label>Fig. 1</label><caption><p>Hit compound obtained from HTS.</p></caption><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="p0020">All series of 3-acyl-2-amino-1,4-dihydroquinolin-4-one analogues were synthesized using <xref rid="f0010" ref-type="fig">Scheme 1</xref>. β-Keto amides <bold>2</bold> were prepared either by reaction of diketene and anilines in the presence of basic catalyst or condensation reaction of substituted-acetyl acetate and anilines. Bis(methylthio) compounds <bold>3</bold> were synthesized by reacting β-keto amides <bold>2</bold> with carbon disulfide and dimethylsulfate in the presence of potassium carbonate. Refluxing bis(methylthio) compounds <bold>3</bold> in an inert solvent like 1,2-dichlorobenzene was transformed into 3-acyl-2-methylsulfanyl-quinoline-4(1<italic>H</italic>)-ones <bold>4</bold>.<xref rid="b0055" ref-type="bibr"><sup>11</sup></xref> Treatment of 3-acyl-2-methylsulfanyl-quinolin-4(1<italic>H</italic>)-ones <bold>4</bold> with hydrogen peroxide in acetic acid leaded to the corresponding sulfoxides <bold>5</bold>, which are more reactive to substitution reaction. Nucleophilic substitution reactions with various amines with sulfoxides <bold>5</bold> afforded 2-amino-1,4-dihydroquinolin-4(1<italic>H</italic>)-ones <bold>6</bold>.<xref rid="b0060" ref-type="bibr"><sup>12</sup></xref><fig id="f0010"><label>Scheme 1</label><caption><p>Synthesis pathway towards derivatives <bold>6</bold>. Reagents and conditions: (a) Diketene, Et<sub>3</sub>N, benzene, 110 °C; or Substituted-acetyl acetate, Et<sub>3</sub>N, toluene, 125 °C; (b) CS<sub>2</sub>, Dimethyl sulfate, n-Bu<sub>4</sub>NBr, K<sub>2</sub>CO<sub>3</sub>, DMF, rt; (c) o-Dichlorobenzene, 180 °C; (d) H<sub>2</sub>O<sub>2</sub>, AcOH, 50 °C; (e) Amines or alcohol, Ph<sub>2</sub>O, 180 °C.</p></caption><graphic xlink:href="gr2_lrg"></graphic></fig></p><p id="p0025">The anti-MERS-CoV activities of the synthesized compounds for Vero cells infected with a Korean clinical MERS-CoV isolate were determined by monitoring the cells expressing viral spike (S) protein using immunofluorescence assay (IFA).<xref rid="b0035" ref-type="bibr"><sup>7</sup></xref> Extensive SAR investigations to assess the effects of 3-acyl moieties, substituents on aryl, and various amines are shown in <xref rid="t0005" ref-type="table">Table 1</xref>.<table-wrap position="float" id="t0005"><label>Table 1</label><caption><p>MERS-CoV inhibitory activity of 3-acyl-2-amino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one derivatives.<fig id="f0015"><graphic xlink:href="fx1_lrg"></graphic></fig></p></caption><table frame="hsides" rules="groups"><thead><tr><th>Cpd</th><th>X</th><th>Y</th><th>Z</th><th>W</th><th>R<sup>1</sup></th><th>R<sup>2</sup></th><th>IC<sub>50</sub> (μM)<xref rid="tblfn1" ref-type="table-fn">a</xref></th><th>CC<sub>50</sub> (μM)<xref rid="tblfn1" ref-type="table-fn">b</xref></th><th>SI<xref rid="tblfn2" ref-type="table-fn">c</xref></th></tr></thead><tbody><tr><td><bold>1</bold></td><td>H</td><td>Cl</td><td>H</td><td>CF<sub>3</sub></td><td>Me</td><td>i-PrNH-</td><td>0.77</td><td>>25</td><td>33</td></tr><tr><td><bold>6a</bold></td><td>H</td><td>H</td><td>H</td><td>i-Pr</td><td>Me</td><td>i-PrNH-</td><td>>25</td><td>–</td><td>–</td></tr><tr><td><bold>6b</bold></td><td>H</td><td>Me</td><td>H</td><td>Me</td><td>Me</td><td>i-PrNH-</td><td>>25</td><td>–</td><td>–</td></tr><tr><td><bold>6c</bold></td><td>H</td><td>Cl</td><td>H</td><td>CF<sub>3</sub></td><td>Ph</td><td>i-PrNH-</td><td>>25</td><td>–</td><td>–</td></tr><tr><td><bold>6d</bold></td><td>H</td><td>Cl</td><td>H</td><td>CF<sub>3</sub></td><td>Me</td><td>2,4-F<sub>2</sub>-PhNH-</td><td>0.15</td><td>7.3</td><td>78</td></tr><tr><td><bold>6e</bold></td><td>H</td><td>Cl</td><td>H</td><td>F</td><td>Me</td><td>2,4-F<sub>2</sub>-PhNH-</td><td>0.98</td><td>>25</td><td>26</td></tr><tr><td><bold>6f</bold></td><td>H</td><td>Cl</td><td>H</td><td>NO<sub>2</sub></td><td>Me</td><td>2,4-F<sub>2</sub>-PhNH-</td><td>1.16</td><td>>25</td><td>21</td></tr><tr><td><bold>6g</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>2,4-F<sub>2</sub>-PhNH-</td><td>1.06</td><td>>25</td><td>25</td></tr><tr><td><bold>6h</bold></td><td>Cl</td><td>Cl</td><td>H</td><td>Cl</td><td>Me</td><td>2,4-F<sub>2</sub>-PhNH-</td><td>0.29</td><td>>25</td><td>91</td></tr><tr><td><bold>6i</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>1-Piperidinyl</td><td>>25</td><td>>25</td><td>1</td></tr><tr><td><bold>6j</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>4-Morpholinyl</td><td>>25</td><td>>25</td><td>1</td></tr><tr><td><bold>6k</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td><italic>n</italic>-ButylNH-</td><td>>25</td><td>>25</td><td>1</td></tr><tr><td><bold>6l</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>3,4-Cl<sub>2</sub>-PhCH<sub>2</sub>O-</td><td>7.8</td><td>>25</td><td>3</td></tr><tr><td><bold>6m</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>2,4-F<sub>2</sub>-PhCH<sub>2</sub>NH-</td><td>5.9</td><td>>25</td><td>3</td></tr><tr><td><bold>6n</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>4-F-PhCH<sub>2</sub>NH-</td><td>17.6</td><td>>25</td><td>1</td></tr><tr><td><bold>6o</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>4-MeO-PhCH<sub>2</sub>NH-</td><td>>25</td><td>>25</td><td>1</td></tr><tr><td><bold>6p</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>3-MeO-PhNH-</td><td>>25</td><td>>25</td><td>1</td></tr><tr><td><bold>6q</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>4-MeO-PhNH-</td><td>>25</td><td>>25</td><td>1</td></tr><tr><td><bold>6r</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>4-Br-PhNH-</td><td>1.13</td><td>>25</td><td>28</td></tr><tr><td><bold>6s</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>4-Cl-PhNH-</td><td>1.44</td><td>>25</td><td>22</td></tr><tr><td><bold>6t</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>Me</td><td>2,3,4-F<sub>3</sub>-PhNH-</td><td>0.53</td><td>>25</td><td>48</td></tr><tr><td><bold>6u</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>i-Pr</td><td>2,3,4-F<sub>3</sub>-PhNH-</td><td>0.086 ± 0.041<xref rid="tblfn3" ref-type="table-fn">d</xref></td><td>>25</td><td>500</td></tr><tr><td><bold>6v</bold></td><td>H</td><td>F</td><td>H</td><td>F</td><td>i-Pr</td><td>2,4-F<sub>2</sub>-PhNH-</td><td>0.79</td><td>>25</td><td>45</td></tr><tr><td><bold>6w</bold></td><td>Cl</td><td>Cl</td><td>H</td><td>Cl</td><td>i-Pr</td><td>2,3,4-F<sub>3</sub>-PhNH-</td><td>0.100 ± 0.023<xref rid="tblfn3" ref-type="table-fn">d</xref></td><td>6.4</td><td>77</td></tr><tr><td><bold>6x</bold></td><td>Cl</td><td>H</td><td>H</td><td>Cl</td><td>i-Pr</td><td>2,3,4-F<sub>3</sub>-PhNH-</td><td>0.166 ± 0.067<xref rid="tblfn3" ref-type="table-fn">d</xref></td><td>10.89 ± 4.29<xref rid="tblfn3" ref-type="table-fn">d</xref></td><td>9</td></tr><tr><td><bold>6y</bold></td><td>Cl</td><td>Cl</td><td>F</td><td>Cl</td><td>i-Pr</td><td>2,4-F<sub>2</sub>-PhNH-</td><td>0.129 ± 0.026<xref rid="tblfn3" ref-type="table-fn">d</xref></td><td>>25</td><td>231</td></tr><tr><td><bold>6z</bold></td><td>H</td><td>Cl</td><td>H</td><td>CF<sub>3</sub></td><td>i-Pr</td><td>2,4-F<sub>2</sub>-PhNH</td><td>0.13</td><td>7.3</td><td>144</td></tr></tbody></table><table-wrap-foot><fn id="tblfn1"><label>a,b</label><p id="np005">IC<sub>50</sub> and CC<sub>50</sub> were derived from the results of at least two independent experiment in VERO.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tblfn2"><label>c</label><p id="np010">SI (selectivity index) = CC<sub>50</sub>/IC<sub>50</sub> for inhibiting MERS-CoV infection.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tblfn3"><label>d</label><p id="np015">Mean ± SD of four independent tests.</p></fn></table-wrap-foot></table-wrap></p><p id="p0030">We started SAR studies by varying the substituents of 5 to 8 positions of quinolone ring of compound <bold>1</bold>, having fixed with acetyl group at 3 position and isopropyl amine at 2 position. Compounds with electron donating groups, such as 8-isopropyl (<bold>6a</bold>) and 6,8-dimethyl (<bold>6b</bold>), showed no inhibitory effects. Application of phenyl substituent at 3 position (<bold>6c</bold>) was detrimental for inhibitory effect. 2,4-Difluoroaniline substituent at 2 position (<bold>6d</bold>) resulted in significant higher activity (IC<sub>50</sub> = 0.15 μM). Given the beneficial effect of 2,4-difluoroaniline at 2 position, we explored the effects of electron-withdrawing groups of left-hand ring of quinolone part of <bold>6d</bold> by preparing analogues <bold>6e</bold>–<bold>6h</bold>. Replacement of the C(8)-trifluoromethyl with fluorine (<bold>6e</bold>) and nitro functionality at 2 position (<bold>6f</bold>) were moderately tolerated (IC<sub>50</sub> = 0.98 and 1.16 μM, respectively). 6,8-Difluoro (<bold>6g</bold>) and 5,6,8-trichloro (<bold>6h</bold>) derivatives also retained the inhibitory effects (IC<sub>50</sub> = 1.06 and 0.29 μM, respectively). This observation showed that electron-withdrawing substituents of left-ring of quinolone scaffold were fruitful to inhibitory activity, while electron-donating substituents were detrimental.</p><p id="p0035">Next, substituent effects at 2 position of 1,4-dihydroquinolin-4(1<italic>H</italic>)-one scaffold were evaluated. Although less active than quinolone derivative <bold>6d</bold> (IC<sub>50</sub> = 0.15 μM) with 6-chloro-8-trifluoromethyl group, 6,8-difluoro substituent analogue <bold>6g</bold> opens the possibility to extensively explore SAR studies via modifications of 2 position. Therefore, we have focused on the optimization of <bold>6g</bold>. 3-Acetyl-6,8-difluoro-1,4-dihydroquinolin-4(1<italic>H</italic>)-ones with piperidine (<bold>6i</bold>) and morpholine (<bold>6j</bold>), <italic>n</italic>-butyl amine (<bold>6k</bold>) at 2 position showed no inhibitory effect. 3,4-Dichlorobenzyl alcohol (<bold>6l</bold>) and 2,4-difluorobenzyl amine (<bold>6m</bold>) were only moderated tolerated (IC<sub>50</sub> = 7.8 and 5.9 μM, respectively), whereas 4-fluorobenzyl amine (<bold>6n</bold>) and 4-methoxybenzyl amine (<bold>6o</bold>) functionalities are detrimental for the binding affinities. Compounds with 3-methoxyaniline (<bold>6p</bold>) and 4-methoxyaniline (<bold>6q</bold>) showed no inhibitory effects, indicating that aniline substituents with electron-donating groups were detrimental. 4-Bromoaniline (<bold>6r</bold>) and 4-chloroaniline group (<bold>6s</bold>) showed similar inhibitory effects (IC<sub>50</sub> = 1.13 and 1.44 μM, respectively) to <bold>6g</bold>. 2,3,4-Trifluoroaniline analogue <bold>6t</bold> displayed increased inhibitory effect (IC<sub>50</sub> = 0.53 μM). Through the investigation into wide range of substituent effects at 2 position, aniline groups with electron-withdrawing substituents showed high binding affinities (0.53–1.44 μM).</p><p id="p0040">In the next phase of optimization, substituent effects at 3 position were investigated. As the benzoyl substituent (<bold>6c</bold>) at 3 position completely abolished activity and pivaloyl group at 3 position blocked the nucleophilic substitution of anilines at 2 position, compounds with isobutyryl substituent at 3 position were deeply examined (<bold>6u</bold>–<bold>z</bold>). 6,8-Difluoro Compound <bold>6u</bold> and <bold>6v</bold>, including 2,3,4-trifluoroaniline and 2,4-difluoro aniline group at 2 position, showed higher inhibitory effects than its corresponding compounds with acetyl group at 3 position (IC<sub>50</sub> = 0.086 and 0.79 μM, respectively). 5,6,8-Trichloro (<bold>6w</bold>) and 5,8-dichloro compound (<bold>6x)</bold> with 2,3,4-trifluoaniline substituent at 2 position also displayed higher inhibitory effects (IC<sub>50</sub> = 0.100 and 0.166 μM, respectively) than their corresponding ones. 5,6,8-Trichloro (<bold>6y</bold>) and 6-chloro,8-trifluoro compound (<bold>6z)</bold> with 2,4-difluoroaniline substituent at 2 position also showed potent biological activities (IC<sub>50</sub> = 0.129 and 0.13 μM, respectively). Of note, all the above compounds except <bold>6d</bold>, <bold>6w</bold>, and <bold>6z</bold> displayed no obvious cytotoxicity (CC<sub>50</sub> > 10 μM).</p><p id="p0045">Compound <bold>6u</bold> was found to be a very potent MERS-CoV inhibitor and evaluated further for its metabolic stability, hERG, cytotoxicity, and <italic>in vivo</italic> pharmacokinetic profile (<xref rid="t0010" ref-type="table">Table 2</xref>). <bold>6u</bold> displays good metabolic stability in human, rat, and mouse liver microsomes. <bold>6u</bold> shows a low hERG binding affinity and no cytotoxicity toward VERO, HFL-1, L929, NIH 3T3, and CHO-K1 cell lines and it exhibits good oral bioavailability of 56% with promising C<sub>max</sub>, T<sub>1/2</sub>, AUC values and clearance.<table-wrap position="float" id="t0010"><label>Table 2</label><caption><p>Data for microsomal stability, hERG, cytotoxicity, and <italic>in vivo</italic> pharmacokinetic profile of <bold>6u</bold>.</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Assay</th><th>Results of <bold>6u</bold></th></tr></thead><tbody><tr><td>Human microsomal stability<xref rid="tblfn4" ref-type="table-fn">a</xref></td><td>52</td></tr><tr><td>Rat microsomal stability<xref rid="tblfn4" ref-type="table-fn">a</xref></td><td>44</td></tr><tr><td>Mouse microsomal stability<xref rid="tblfn4" ref-type="table-fn">a</xref></td><td>35</td></tr><tr><td>hERG<xref rid="tblfn5" ref-type="table-fn">b</xref></td><td>6.9</td></tr><tr><td rowspan="5">Cytotoxicity<xref rid="tblfn6" ref-type="table-fn">c</xref></td><td>VERO: 86.1</td></tr><tr><td>HFL-1: 15.6</td></tr><tr><td>L929: 15.8</td></tr><tr><td>NIH 3 T3: 65.6</td></tr><tr><td>CHO-K1: 6.9</td></tr><tr><td>In vivo PK<xref rid="tblfn7" ref-type="table-fn">d</xref></td><td></td></tr><tr><td> C<sub>max</sub> (μg/mL)</td><td>2.32 ± 0.20</td></tr><tr><td> T<sub>1/2</sub> (h), i.v.</td><td>4.6 ± 0.66</td></tr><tr><td> AUC<sub>0−24h</sub> (μg·h/mL), i.v.</td><td>28.3 ± 4.18</td></tr><tr><td> AUC<sub>0−∞</sub> (μg·h/mL), i.v.</td><td>28.9 ± 4.21</td></tr><tr><td> CL (L/h/kg), i.v.</td><td>0.07 ± 0.01</td></tr><tr><td> %F</td><td>56</td></tr></tbody></table><table-wrap-foot><fn id="tblfn4"><label>a</label><p id="np020">% original compound remained after 30 min incubation.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tblfn5"><label>b</label><p id="np025">IC<sub>50</sub> (µM) values (binding assay).</p></fn></table-wrap-foot><table-wrap-foot><fn id="tblfn6"><label>c</label><p id="np030">IC<sub>50</sub> (μM) values in various mammalian cell lines. Cell information. VERO: African green monkey kidney cell line, HFL-1: human embryonic lung cell line, L929: mouse fibroblast cell line, NIH 3T3: mouse embryonic fibroblast cell line, CHO-K1: Chinese hamster ovary cell line.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tblfn7"><label>d</label><p id="np035">Data were generated in rats from three determinations, and dosed at 2 mg/kg for i.v. and at 5 mg/kg for p.o. (n = 3).</p></fn></table-wrap-foot></table-wrap></p><p id="p0050">In Summary, we have developed a novel class of 3-acyl-2-amino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one based MERS-CoV inhibitors through systemic SAR optimization from lead compound <bold>1</bold>. Compound <bold>6u</bold>, including isobutyryl substituent at 3 position and 6,8-difluorophenyl group, is a good MERS-CoV inhibitor with IC<sub>50</sub> of 86 nM. In addition, this substance shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good <italic>in vivo</italic> PK properties with an oral bioavailability of 56% in rat. Future optimization of these 3-acyl-2-amino-1,4-dihydroquinolin-4(1<italic>H</italic>)-one based MERS-CoV inhibitors on the <italic>in vivo</italic> efficacy of <bold>6u</bold> in animal models will mainly be performed in due course.</p><sec sec-type="COI-statement"><title>Declaration of Competing Interest</title><p id="p0055">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</p></sec></body><back><ref-list id="bi005"><title>References</title><ref id="b0005"><label>1</label><element-citation publication-type="journal" id="h0005"><person-group person-group-type="author"><name><surname>Cotten</surname><given-names>M.</given-names></name><name><surname>Watson</surname><given-names>S.J.</given-names></name><name><surname>Zumla</surname><given-names>A.I.</given-names></name></person-group><source>mBio</source><volume>5</volume><year>2014</year><fpage>e01062</fpage><lpage>e01063</lpage><pub-id pub-id-type="pmid">24549846</pub-id></element-citation></ref><ref id="b0010"><label>2</label><element-citation publication-type="journal" id="h0010"><person-group person-group-type="author"><name><surname>Liang</surname><given-names>R.</given-names></name><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Zhang</surname><given-names>N.</given-names></name></person-group><source>Viruses</source><volume>10</volume><year>2018</year><fpage>721</fpage></element-citation></ref><ref id="b0015"><label>3</label><element-citation publication-type="journal" id="h0015"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>J.F.W.</given-names></name><name><surname>Lau</surname><given-names>S.K.P.</given-names></name><name><surname>To</surname><given-names>K.K.W.</given-names></name><name><surname>Cheng</surname><given-names>V.C.C.</given-names></name><name><surname>Woo</surname><given-names>P.C.Y.</given-names></name><name><surname>Yuen</surname><given-names>K.-Y.</given-names></name></person-group><source>Clin Microbiol Rev</source><volume>28</volume><year>2015</year><fpage>465</fpage><pub-id pub-id-type="pmid">25810418</pub-id></element-citation></ref><ref id="b0020"><label>4</label><element-citation publication-type="journal" id="h0020"><person-group person-group-type="author"><name><surname>De Wit</surname><given-names>E.</given-names></name><name><surname>van Doremalen</surname><given-names>N.</given-names></name><name><surname>Falzarano</surname><given-names>D.</given-names></name><name><surname>Munster</surname><given-names>V.J.</given-names></name></person-group><source>Nat Rev Microbiol</source><volume>14</volume><year>2016</year><fpage>523</fpage><pub-id pub-id-type="pmid">27344959</pub-id></element-citation></ref><ref id="b0025"><label>5</label><element-citation publication-type="journal" id="h0025"><person-group person-group-type="author"><name><surname>Dyall</surname><given-names>J.</given-names></name><name><surname>Coleman</surname><given-names>C.M.</given-names></name><name><surname>Hart</surname><given-names>B.J.</given-names></name></person-group><source>Antimicrob Agents Chemother</source><volume>58</volume><issue>8</issue><year>2014</year><fpage>4885</fpage><pub-id pub-id-type="pmid">24841273</pub-id></element-citation></ref><ref id="b0030"><label>6</label><element-citation publication-type="journal" id="h0030"><person-group person-group-type="author"><name><surname>de Wilde</surname><given-names>A.H.</given-names></name><name><surname>Jochmans</surname><given-names>D.</given-names></name><name><surname>Posthuma</surname><given-names>C.C.</given-names></name></person-group><source>Antimicrob Agents Chemother</source><volume>58</volume><issue>8</issue><year>2014</year><fpage>4875</fpage><pub-id pub-id-type="pmid">24841269</pub-id></element-citation></ref><ref id="b0035"><label>7</label><element-citation publication-type="journal" id="h0035"><label>(a)</label><person-group person-group-type="author"><name><surname>Cruz</surname><given-names>D.J.</given-names></name><name><surname>Bonotto</surname><given-names>R.M.</given-names></name><name><surname>Gomes</surname><given-names>R.G.</given-names></name></person-group><source>PLoS Negl Trop Dis</source><volume>7</volume><issue>10</issue><year>2013</year><fpage>2471</fpage></element-citation><mixed-citation publication-type="other" id="h0040"><label>(b)</label>Anti-MERS-CoV activity assay. Vero cells were seeded in 384-well µ-clear plates (Greiner Bio-One, Austria) at a density of 1.2 × 10<sup>4</sup> cell per well in 30 µl SFM and incubated for 24 h prior to infection. Compounds were transferred from the library into intermediate 384-well polypropylene plates containing SFM and were mixed using an automated liquid handling system (Apricot Personal Pipettor, Apricot Design, USA). Subsequently, the diluted compounds were added to the cell plates in 10 µl volumes (final DMSO concentration of 0.5% (v/v)). For infection, the plates were transferred into the BSL-3 containment facility prior to adding 10 µl MERS-CoV at a multiplicity of infection (MOI) of 0.0625. The cells were fixed at 24 hpi with 4% PFA and the infected cells were identified by IFA. The fixed cells were permeabilized with 0.25% Triton X-100 (Sigma-Aldrich, USA) for 20 min. Then the cells were incubated with rabbit anti-MERS-CoV Spike antibody for 1 h at 37°C. After three washes with PBS, the cells were incubated with Alexa 488-conjugated goat anti-rabbit IgG (H + L) secondary antibody and Hoechst 33342 (Life Technologies, USA) for 1 h at 37°C. Images were acquired by Perkin Elmer Operetta (20×; Waltham, USA). The acquired images were analyzed with in-house-developed Image-Mining 3.0 (IM 3.0) plug-in software. In the analyzed image, the total number of cells and the number of infected cells were determined by counting Hoechst-stained nuclei and spike protein-expressing cells, respectively.</mixed-citation></ref><ref id="b0040"><label>8</label><element-citation publication-type="journal" id="h0045"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>H.J.</given-names></name><name><surname>Kim</surname><given-names>N.</given-names></name><name><surname>Shum</surname><given-names>D.</given-names></name><name><surname>Huddar</surname><given-names>S.</given-names></name><name><surname>Park</surname><given-names>C.M.</given-names></name><name><surname>Jang</surname><given-names>S.</given-names></name></person-group><source>Assay Drug Dev Techn</source><volume>15</volume><issue>5</issue><year>2017</year><fpage>198</fpage></element-citation></ref><ref id="b0045"><label>9</label><element-citation publication-type="journal" id="h0050"><person-group person-group-type="author"><name><surname>Kang</surname><given-names>D.-H.</given-names></name><name><surname>Jun</surname><given-names>K.-Y.</given-names></name><name><surname>Lee</surname><given-names>J.P.</given-names></name><name><surname>Pak</surname><given-names>C.S.</given-names></name><name><surname>Na</surname><given-names>Y.</given-names></name><name><surname>Kwon</surname><given-names>Y.</given-names></name></person-group><source>J Med Chem</source><volume>52</volume><issue>9</issue><year>2009</year><fpage>3093</fpage><pub-id pub-id-type="pmid">19419206</pub-id></element-citation></ref><ref id="b0050"><label>10</label><element-citation publication-type="journal" id="h0055"><person-group person-group-type="author"><name><surname>Sharma</surname><given-names>M.C.</given-names></name><name><surname>Sharma</surname><given-names>S.</given-names></name></person-group><source>Med Chem Res</source><volume>25</volume><year>2016</year><fpage>2119</fpage></element-citation></ref><ref id="b0055"><label>11</label><element-citation publication-type="journal" id="h0060"><label>(a)</label><person-group person-group-type="author"><name><surname>Park</surname><given-names>C.S.</given-names></name><name><surname>Choi</surname><given-names>E.B.</given-names></name></person-group><source>Synthesis</source><volume>12</volume><year>1992</year><fpage>1291</fpage></element-citation><element-citation publication-type="journal" id="h0065"><label>(b)</label><person-group person-group-type="author"><name><surname>Choi</surname><given-names>E.B.</given-names></name><name><surname>Yeon</surname><given-names>G.H.</given-names></name><name><surname>Lee</surname><given-names>H.K.</given-names></name><name><surname>Yang</surname><given-names>H.C.</given-names></name><name><surname>Yoo</surname><given-names>C.Y.</given-names></name><name><surname>Park</surname><given-names>C.S.</given-names></name></person-group><source>Synthesis</source><volume>18</volume><year>2003</year><fpage>2771</fpage></element-citation><mixed-citation publication-type="other" id="h0070"><label>(c)</label><bold>6u</bold>: <sup>1</sup>H NMR (300 MHz, CDCl<sub>3</sub>) δ 13.45 (s, 1H), 7.80 (dt, <italic>J</italic> = 8.8, 2.2 Hz, 1H), 7.62 (s, 1H), 7.24–7.15 (m, 2H), 7.10 (ddd, <italic>J</italic> = 10.3, 7.8, 2.8 Hz, 1H), 4.48–4.28 (m, 1H), 1.21 (d, <italic>J</italic> = 6.7 Hz, 6H); <sup>13</sup>C NMR (500 MHz, CDCl<sub>3</sub>) δ 209.41, 174.51, 159.10, 157.13, 154.38, 151.00, 149.81, 149.02, 127.14, 121.55, 119.85, 113.32, 108.23, 107.16, 106.93, 100.62, 38.98, 19.17; HRMS <italic>m/e</italic> calcd for C<sub>19</sub>H<sub>13</sub>F<sub>5</sub>N<sub>2</sub>O<sub>2</sub> [M]<sup>+</sup> 396.0897; found 396.0910.</mixed-citation></ref><ref id="b0060"><label>12</label><element-citation publication-type="journal" id="h0075"><person-group person-group-type="author"><name><surname>Hwang</surname><given-names>B.H.</given-names></name><name><surname>Park</surname><given-names>S.H.</given-names></name><name><surname>Choi</surname><given-names>E.B.</given-names></name><name><surname>Park</surname><given-names>C.S.</given-names></name><name><surname>Lee</surname><given-names>H.K.</given-names></name></person-group><source>Tetrahedron</source><volume>64</volume><year>2008</year><fpage>6698</fpage></element-citation></ref></ref-list><sec id="s0010" sec-type="supplementary-material"><label>Appendix A</label><title>Supplementary data</title><p id="p0070">The following are the Supplementary data to this article:<supplementary-material content-type="local-data" id="m0005"><caption><title>Supplementary data 1</title></caption><media xlink:href="mmc1.docx"></media></supplementary-material></p></sec><ack id="ak005"><title>Acknowledgements</title><p>The chemical library used in this study was kindly provided by Korea Chemical Bank (<ext-link ext-link-type="uri" xlink:href="http://www.chemicalbank.org/" id="ir005">http://www.chemicalbank.org/</ext-link>) of <funding-source id="gp010">Korea Research Institute of Chemical Technology</funding-source>. This work was supported by a grant of <funding-source id="gp005">National Research Council of Science & Technology</funding-source> (NST) by the Korean government (MSIP) (No. CRC-16-01-KRICT).</p></ack><fn-group><fn id="s0005" fn-type="supplementary-material"><label>Appendix A</label><p id="p0065">Supplementary data to this article can be found online at <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.bmcl.2019.126727" id="ir010">https://doi.org/10.1016/j.bmcl.2019.126727</ext-link>.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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