{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:08:54Z","timestamp":1790665734701,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["284237345 - KFO309"],"award-info":[{"award-number":["284237345 - KFO309"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2019,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad\u2010spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub\u2010nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6\/P5\u2010P1 segments, which directly interact with furin. The cyclic derivatives together with two non\u2010cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.<\/jats:p>","DOI":"10.1002\/cmdc.201800807","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T04:47:30Z","timestamp":1548391650000},"page":"673-685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Design, Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin"],"prefix":"10.1002","volume":"14","author":[{"given":"Thuy","family":"Van Lam\u2005van","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelia","family":"Hardes","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Ruth","family":"Heindl","sequence":"additional","affiliation":[{"name":"Institute of Virology Philipps University  Hans-Meerwein-Str. 2 35043 Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory E.","family":"Morty","sequence":"additional","affiliation":[{"name":"Department of Lung Development and Remodelling Max Planck Institute for Heart and Lung Research  Bad Nauheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"B\u00f6ttcher\u2010Friebertsh\u00e4user","sequence":"additional","affiliation":[{"name":"Institute of Virology Philipps University  Hans-Meerwein-Str. 2 35043 Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology University of Maryland Medical School  Baltimore MD 21201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel E.","family":"Than","sequence":"additional","affiliation":[{"name":"Protein Crystallography Group Leibniz Institute on Aging\u2014Fritz Lipmann Institute  Beutenbergstr. 11 07745 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven O.","family":"Dahms","sequence":"additional","affiliation":[{"name":"Department of Biosciences University of Salzburg  Billrothstrasse 11 5020 Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-4754","authenticated-orcid":false,"given":"Torsten","family":"Steinmetzer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.10.003"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2018.1454428"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00506-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00788"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00469"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.04.008"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01460"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm3012917"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00606"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm934"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3699"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/BMC.2011.034"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:HIJO.0000032358.51866.a2"},{"key":"e_1_2_8_14_1","first-page":"148651","author":"Declercq J.","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28713-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130417"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2017.04.001"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201500447"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b01124"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700108"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb3005275"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja503710n"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/b719950c"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201500103"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9012455"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/co300136j"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.06.091"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(79)63019-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700596"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb500087x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613630113"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18030556"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151098198"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102633200"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306949200"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.332643"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.05.006"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2017.1306521"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.018"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.15171\/bi.2017.17"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2013.01.011"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.01.111"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm970832g"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0909049512009715"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1088\/1742-6596\/425\/1\/012001"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576716004416"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909052925"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904011679"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-3-63"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201800807","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201800807","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.201800807","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201800807","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T16:47:23Z","timestamp":1760287643000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201800807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,20]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,3,22]]}},"alternative-id":["10.1002\/cmdc.201800807"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201800807","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,20]]},"assertion":[{"value":"2018-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}