{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:42:00Z","timestamp":1780058520276,"version":"3.54.0"},"reference-count":52,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T00:00:00Z","timestamp":1458086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","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":[[2016,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the significant progress achieved with combination antiretroviral therapy in the fight against human immunodeficiency virus (HIV) infection, the difficulty to eradicate the virus together with the rapid emergence of multidrug\u2010resistant strains clearly underline a pressing need for innovative agents, possibly endowed with novel mechanisms of action. In this context, owing to its essential role in HIV genome replication, the reverse transcriptase associated ribonuclease\u2005H (RNase\u2005H) has proven to be an appealing target. To identify new RNase\u2005H inhibitors, an in\u2010house cycloheptathiophene\u20103\u2010carboxamide library was screened; this led to compounds endowed with inhibitory activity, the structural optimization of which led to the catechol derivative 2\u2010(3,4\u2010dihydroxybenzamido)\u2010<jats:italic>N<\/jats:italic>\u2010(pyridin\u20102\u2010yl)\u20105,6,7,8\u2010tetrahydro\u20104<jats:italic>H<\/jats:italic>\u2010cyclohepta[<jats:italic>b<\/jats:italic>]thiophene\u20103\u2010carboxamide (compound <jats:bold>33<\/jats:bold>) with an IC<jats:sub>50<\/jats:sub> value on the RNase\u2005H activity in the nanomolar range. Mechanistic studies suggested selective inhibition of the RNase\u2005H through binding to an innovative allosteric site, which could be further exploited to enrich this class of inhibitors.<\/jats:p>","DOI":"10.1002\/cmdc.201600015","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T22:07:15Z","timestamp":1458338835000},"page":"1709-1720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Studies on Cycloheptathiophene\u20103\u2010carboxamide Derivatives as Allosteric HIV\u20101 Ribonuclease\u2005H Inhibitors"],"prefix":"10.1002","volume":"11","author":[{"given":"Angela","family":"Corona","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze della Vita e dell'Ambiente Cittadella Universitaria di Monserrato  SS554 09042 Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Desantis","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Perugia  Via del Liceo\u20051 06123 Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Massari","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Perugia  Via del Liceo\u20051 06123 Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Distinto","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e dell'Ambiente Cittadella Universitaria di Monserrato  SS554 09042 Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Masaoka","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory National Cancer Institute  Frederick MD 21702-1201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Perugia  Via del Liceo\u20051 06123 Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Esposito","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e dell'Ambiente Cittadella Universitaria di Monserrato  SS554 09042 Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Manfroni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Perugia  Via del Liceo\u20051 06123 Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Maccioni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e dell'Ambiente Cittadella Universitaria di Monserrato  SS554 09042 Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta","family":"Cecchetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Perugia  Via del Liceo\u20051 06123 Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Pannecouque","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy Department of Microbiology and Immunology Rega Institute for Medical Research\u2014KU Leuven  Minderbroedersstraat 10 3000 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart F. J.","family":"Le\u2005Grice","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory National Cancer Institute  Frederick MD 21702-1201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Tramontano","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e dell'Ambiente Cittadella Universitaria di Monserrato  SS554 09042 Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana","family":"Tabarrini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Perugia  Via del Liceo\u20051 06123 Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,16]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-407"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094495"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/fvl.14.24"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)81559-5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/586401"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.178"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03605-14"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501799k"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.02.032"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm2000757"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4IB00111G"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb600303y"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08057.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000343101"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201402015"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb8001039"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00434-10"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.314781"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400405z"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2485"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.10.208"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201000267"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319100010"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201100073"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01183"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","unstructured":"P. Zhan C. Pannecouque E. De\u2005Clercq X. Liu J. Med. Chem.2015 DOI:10.1021\/acs.jmedchem.5b00497.","DOI":"10.1021\/acs.jmedchem.5b00497"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401560v"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00012"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cber.19660990116"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570360203"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2004.05.100"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.1222"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030644s"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050540c"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.6.1449"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci200194w"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301271j"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.05.006"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(82)87028-6"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)62015-X"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm5001503"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12051"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-015-4652-0"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-058-8_19"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.517"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(88)90134-6"},{"key":"e_1_2_6_47_1","unstructured":"Schr\u00f6dinger Release 2015-2: Maestro version 10.2 Schr\u00f6dinger LLC New York NY (USA) 2015."},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<520::AID-JCC2>3.0.CO;2-W"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0898-5529(88)90015-2"},{"key":"e_1_2_6_50_1","unstructured":"Glide version\u20055.9 Schr\u00f6dinger LLC New York NY (USA) 2013."},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00470-9"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar000033j"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201600015","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201600015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T08:27:39Z","timestamp":1760257659000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201600015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,16]]},"references-count":52,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2016,8,19]]}},"alternative-id":["10.1002\/cmdc.201600015"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201600015","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,16]]},"assertion":[{"value":"2016-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}