{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:34:22Z","timestamp":1786988062626,"version":"build-2736575974"},"reference-count":27,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009108","name":"Shandong University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014103","name":"Key Technology Research and Development Program of Shandong","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","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":[[2020,5]]},"DOI":"10.1016\/j.ejmech.2020.112237","type":"journal-article","created":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T11:32:48Z","timestamp":1584185568000},"page":"112237","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":30,"special_numbering":"C","title":["In situ click chemistry-based rapid discovery of novel HIV-1 NNRTIs by exploiting the hydrophobic channel and tolerant regions of NNIBP"],"prefix":"10.1016","volume":"193","author":[{"given":"Dongwei","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenju","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaochan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"De Clercq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Pannecouque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2020.112237_bib2","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1021\/acs.jmedchem.5b00497","article-title":"Anti-HIV drug discovery and development: current innovations and future trends","volume":"59","author":"Zhan","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s42004-019-0174-8","article-title":"Discovery of piperidine-substituted thiazolo[5,4-d]pyrimidine derivatives as potent and orally bioavailable HIV-1 non-nucleoside reverse transcriptase inhibitors","volume":"2","author":"Kang","year":"2019","journal-title":"Commun. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib4","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1021\/acs.jmedchem.8b01656","article-title":"Identification of dihydrofuro[3,4-d]pyrimidine derivatives as novel HIV-1 non-nucleoside reverse transcriptase inhibitors with promising antiviral activities and desirable physicochemical properties","volume":"62","author":"Kang","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib5","doi-asserted-by":"crossref","first-page":"9743","DOI":"10.1021\/ja4018418","article-title":"Thermodynamics of HIV-1 reverse transcriptase in action elucidates the mechanism of action of non-nucleoside inhibitors","volume":"135","author":"Bec","year":"2013","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2020.112237_bib6","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.1021\/acs.jmedchem.8b00843","article-title":"The journey of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) from lab to clinic","volume":"62","author":"Namasivayam","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib7","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1021\/acs.jmedchem.9b01769","article-title":"Discovery and characterization of fluorine-substituted diarylpyrimidine derivatives as novel HIV-1 NNRTIs with highly improved resistance profiles and low activity for the hERG ion channel","volume":"63","author":"Kang","year":"2020","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib8","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1056\/NEJMp1710608","article-title":"HIV drug resistance - an emerging threat to epidemic control","volume":"377","author":"Beyrer","year":"2017","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ejmech.2020.112237_bib9","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1080\/17425255.2019.1673367","article-title":"Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 treatment","volume":"15","author":"Wang","year":"2019","journal-title":"Expet Opin. Drug Metabol. Toxicol."},{"key":"10.1016\/j.ejmech.2020.112237_bib10","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1021\/ar800236t","article-title":"Efficient drug lead discovery and optimization","volume":"42","author":"Jorgensen","year":"2009","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.ejmech.2020.112237_bib11","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41586-019-1589-1","article-title":"Modular click chemistry libraries for functional screens using a diazotizing reagent","volume":"574","author":"Meng","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2020.112237_bib12","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.drudis.2015.08.004","article-title":"Discovery of bioactive molecules from CuAAC click-chemistry-based combinatorial libraries","volume":"21","author":"Wang","year":"2016","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejmech.2020.112237_bib13","doi-asserted-by":"crossref","first-page":"9562","DOI":"10.1021\/jm300837y","article-title":"Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries","volume":"55","author":"Suzuki","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib14","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.ejmech.2018.04.008","article-title":"Harnessing pyrrolidine iminosugars into dimeric structures for the rapid discovery of divalent glycosidase inhibitors","volume":"151","author":"Carmona","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib15","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1080\/17460441.2019.1614910","article-title":"Recent applications of click chemistry in drug discovery","volume":"14","author":"Jiang","year":"2019","journal-title":"Expet Opin. Drug Discov."},{"key":"10.1016\/j.ejmech.2020.112237_bib16","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1016\/j.bmcl.2016.09.071","article-title":"First discovery of novel 3-hydroxy-quinazoline-2,4(1H,3H)-diones as specific anti-vaccinia and adenovirus agents via \u2019privileged scaffold\u2019 refining approach","volume":"26","author":"Kang","year":"2016","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2020.112237_bib17","doi-asserted-by":"crossref","first-page":"111696","DOI":"10.1016\/j.ejmech.2019.111696","article-title":"Identification of highly potent and selective Cdc 25 protein phosphatases inhibitors from miniaturization click-chemistry-based combinatorial libraries","volume":"183","author":"Jing","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.ejmech.2018.09.029","article-title":"Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library","volume":"158","author":"Wu","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib19","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1080\/17460441.2016.1210125","article-title":"Discovery of novel anti-HIV agents via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry-based approach","volume":"11","author":"Gao","year":"2016","journal-title":"Expet Opin. Drug Discov."},{"key":"10.1016\/j.ejmech.2020.112237_bib20","doi-asserted-by":"crossref","first-page":"7991","DOI":"10.1021\/acs.jmedchem.6b00738","article-title":"Design, synthesis, and evaluation of thiophene[3,2-d]pyrimidine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors with significantly improved drug resistance profiles","volume":"59","author":"Kang","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib21","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.36340","article-title":"Structural basis for potent and broad inhibition of HIV-1 RT by thiophene[3,2-d]pyrimidine non-nucleoside inhibitors","volume":"7","author":"Yang","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.ejmech.2020.112237_bib22","article-title":"Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs","author":"Kang","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.ejmech.2020.112237_bib23","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1039\/C9OB00032A","article-title":"Targeting the hydrophobic channel of NNIBP: discovery of novel 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs with high potency against wild-type and K103N mutant virus","volume":"17","author":"Zhou","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib24","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1021\/acs.jmedchem.8b01729","volume":"62","author":"Huang","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib25","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ejmech.2018.03.059","article-title":"Targeting the entrance channel of NNIBP: discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus","volume":"151","author":"Tian","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib26","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.1021\/acs.jmedchem.7b00332","article-title":"Structure-based optimization of thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors with improved potency against resistance-associated variants","volume":"60","author":"Kang","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112237_bib27","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1124\/jpet.105.093393","article-title":"Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs","volume":"316","author":"Katchman","year":"2006","journal-title":"J.\u00a0Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejmech.2020.112237_bib28","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nprot.2007.517","article-title":"Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later","volume":"3","author":"Pannecouque","year":"2008","journal-title":"Nat. Protoc."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342030204X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342030204X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:08:43Z","timestamp":1759327723000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352342030204X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":27,"alternative-id":["S022352342030204X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2020.112237","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2020,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In situ click chemistry-based rapid discovery of novel HIV-1 NNRTIs by exploiting the hydrophobic channel and tolerant regions of NNIBP","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2020.112237","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"112237"}}