{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:40:51Z","timestamp":1788716451060,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82173677"],"award-info":[{"award-number":["82173677"]}]},{"name":"National Natural Science Foundation of China","award":["81773574"],"award-info":[{"award-number":["81773574"]}]},{"name":"National Natural Science Foundation of China","award":["81420108027"],"award-info":[{"award-number":["81420108027"]}]},{"name":"National Natural Science Foundation of China","award":["2019JZZY021011"],"award-info":[{"award-number":["2019JZZY021011"]}]},{"name":"National Natural Science Foundation of China","award":["ZR2020JQ31"],"award-info":[{"award-number":["ZR2020JQ31"]}]},{"name":"National Natural Science Foundation of China","award":["R01AI150491"],"award-info":[{"award-number":["R01AI150491"]}]},{"name":"National Natural Science Foundation of China","award":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"],"award-info":[{"award-number":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"]}]},{"name":"Key Project of NSFC for International Cooperation","award":["82173677"],"award-info":[{"award-number":["82173677"]}]},{"name":"Key Project of NSFC for International Cooperation","award":["81773574"],"award-info":[{"award-number":["81773574"]}]},{"name":"Key Project of NSFC for International Cooperation","award":["81420108027"],"award-info":[{"award-number":["81420108027"]}]},{"name":"Key Project of NSFC for International Cooperation","award":["2019JZZY021011"],"award-info":[{"award-number":["2019JZZY021011"]}]},{"name":"Key Project of NSFC for International Cooperation","award":["ZR2020JQ31"],"award-info":[{"award-number":["ZR2020JQ31"]}]},{"name":"Key Project of NSFC for International Cooperation","award":["R01AI150491"],"award-info":[{"award-number":["R01AI150491"]}]},{"name":"Key Project of NSFC for International Cooperation","award":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"],"award-info":[{"award-number":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"]}]},{"name":"Shandong Provincial Key Research and Development Project","award":["82173677"],"award-info":[{"award-number":["82173677"]}]},{"name":"Shandong Provincial Key Research and Development Project","award":["81773574"],"award-info":[{"award-number":["81773574"]}]},{"name":"Shandong Provincial Key Research and Development Project","award":["81420108027"],"award-info":[{"award-number":["81420108027"]}]},{"name":"Shandong Provincial Key Research and Development Project","award":["2019JZZY021011"],"award-info":[{"award-number":["2019JZZY021011"]}]},{"name":"Shandong Provincial Key Research and Development Project","award":["ZR2020JQ31"],"award-info":[{"award-number":["ZR2020JQ31"]}]},{"name":"Shandong Provincial Key Research and Development Project","award":["R01AI150491"],"award-info":[{"award-number":["R01AI150491"]}]},{"name":"Shandong Provincial Key Research and Development Project","award":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"],"award-info":[{"award-number":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"]}]},{"name":"Science Foundation for Outstanding Young Scholars of Shandong Province","award":["82173677"],"award-info":[{"award-number":["82173677"]}]},{"name":"Science Foundation for Outstanding Young Scholars of Shandong Province","award":["81773574"],"award-info":[{"award-number":["81773574"]}]},{"name":"Science Foundation for Outstanding Young Scholars of Shandong Province","award":["81420108027"],"award-info":[{"award-number":["81420108027"]}]},{"name":"Science Foundation for Outstanding Young Scholars of Shandong Province","award":["2019JZZY021011"],"award-info":[{"award-number":["2019JZZY021011"]}]},{"name":"Science Foundation for Outstanding Young Scholars of Shandong Province","award":["ZR2020JQ31"],"award-info":[{"award-number":["ZR2020JQ31"]}]},{"name":"Science Foundation for Outstanding Young Scholars of Shandong Province","award":["R01AI150491"],"award-info":[{"award-number":["R01AI150491"]}]},{"name":"Science Foundation for Outstanding Young Scholars of Shandong Province","award":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"],"award-info":[{"award-number":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"]}]},{"name":"NIH\/NIAID","award":["82173677"],"award-info":[{"award-number":["82173677"]}]},{"name":"NIH\/NIAID","award":["81773574"],"award-info":[{"award-number":["81773574"]}]},{"name":"NIH\/NIAID","award":["81420108027"],"award-info":[{"award-number":["81420108027"]}]},{"name":"NIH\/NIAID","award":["2019JZZY021011"],"award-info":[{"award-number":["2019JZZY021011"]}]},{"name":"NIH\/NIAID","award":["ZR2020JQ31"],"award-info":[{"award-number":["ZR2020JQ31"]}]},{"name":"NIH\/NIAID","award":["R01AI150491"],"award-info":[{"award-number":["R01AI150491"]}]},{"name":"NIH\/NIAID","award":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"],"award-info":[{"award-number":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"]}]},{"name":"Department of Science &amp; Technology","award":["82173677"],"award-info":[{"award-number":["82173677"]}]},{"name":"Department of Science &amp; Technology","award":["81773574"],"award-info":[{"award-number":["81773574"]}]},{"name":"Department of Science &amp; Technology","award":["81420108027"],"award-info":[{"award-number":["81420108027"]}]},{"name":"Department of Science &amp; Technology","award":["2019JZZY021011"],"award-info":[{"award-number":["2019JZZY021011"]}]},{"name":"Department of Science &amp; Technology","award":["ZR2020JQ31"],"award-info":[{"award-number":["ZR2020JQ31"]}]},{"name":"Department of Science &amp; Technology","award":["R01AI150491"],"award-info":[{"award-number":["R01AI150491"]}]},{"name":"Department of Science &amp; Technology","award":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"],"award-info":[{"award-number":["DST\/INT\/BRICS\/COVID-19\/2020-Part-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>As a key structural protein, HIV capsid (CA) protein plays multiple roles in the HIV life cycle, and is considered a promising target for anti-HIV treatment. Based on the structural information of CA modulator PF-74 bound to HIV-1 CA hexamer, 18 novel phenylalanine derivatives were synthesized via the Ugi four-component reaction. In vitro anti-HIV activity assays showed that most compounds exhibited low-micromolar-inhibitory potency against HIV. Among them, compound I-19 exhibited the best anti-HIV-1 activity (EC50 = 2.53 \u00b1 0.84 \u03bcM, CC50 = 107.61 \u00b1 27.43 \u03bcM). In addition, I-14 displayed excellent HIV-2 inhibitory activity (EC50 = 2.30 \u00b1 0.11 \u03bcM, CC50 &gt; 189.32 \u03bcM) with relatively low cytotoxicity, being more potent than that of the approved drug nevirapine (EC50 &gt; 15.02 \u03bcM, CC50 &gt; 15.2 \u03bcM). Additionally, surface plasmon resonance (SPR) binding assays demonstrated direct binding to the HIV CA protein. Moreover, molecular docking and molecular dynamics simulations provided additional information on the binding mode of I-19 to HIV-1 CA. In summary, we further explored the structure\u2014activity relationships (SARs) and selectivity of anti-HIV-1\/HIV-2 of PF-74 derivatives, which is conducive to discovering efficient anti-HIV drugs.<\/jats:p>","DOI":"10.3390\/molecules27185995","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T23:16:36Z","timestamp":1663197396000},"page":"5995","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design, Synthesis and Structure\u2014Activity Relationships of Phenylalanine-Containing Peptidomimetics as Novel HIV-1 Capsid Binders Based on Ugi Four-Component Reaction"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiangkai","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem","family":"Sharma","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2133-8847","authenticated-orcid":false,"given":"Brijesh","family":"Rathi","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lide","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9232-953X","authenticated-orcid":false,"given":"Dongwei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"},{"name":"China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2985-8890","authenticated-orcid":false,"given":"Erik","family":"De Clercq","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapym, Rega Institute for Medical Research, K.U. Leuven, Herestraat 49 Postbus 1043 (09.A097), B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-741X","authenticated-orcid":false,"given":"Simon","family":"Cocklin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Pannecouque","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapym, Rega Institute for Medical Research, K.U. Leuven, Herestraat 49 Postbus 1043 (09.A097), B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0580-1897","authenticated-orcid":false,"given":"Alexej","family":"Dick","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-2214","authenticated-orcid":false,"given":"Xinyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"},{"name":"China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"},{"name":"China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province, 44 West Culture Road, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.bcp.2012.12.011","article-title":"Antivirals: Past, present and future","volume":"85","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e01299-18","DOI":"10.1128\/AAC.01299-18","article-title":"In vitro antiviral activity of cabotegravir against HIV-2","volume":"62","author":"Smith","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.antiviral.2013.01.007","article-title":"Molecular basis of human immunodeficiency virus type 1 drug resistance: Overview and recent developments","volume":"98","year":"2013","journal-title":"Antiviral Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1107\/S1744309113011871","article-title":"A triclinic crystal structure of the carboxy-terminal domain of HIV-1 capsid protein with four molecules in the asymmetric unit reveals a novel packing interface","volume":"69","author":"Lamoel","year":"2013","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1021\/acs.biochem.6b00159","article-title":"HIV capsid assembly, mechanism, and structure","volume":"55","author":"Chen","year":"2016","journal-title":"Biochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12977-016-0262-0","article-title":"HIV-1 capsid is involved in post-nuclear entry steps","volume":"13","author":"Chen","year":"2016","journal-title":"Retrovirology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2013.11.002","article-title":"The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells","volume":"39","author":"Lahaye","year":"2013","journal-title":"Immunity"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.tim.2017.04.004","article-title":"Capsid-dependent host factors in HIV-1 infection","volume":"25","author":"Yamashita","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cell.2009.04.063","article-title":"X-ray structures of the hexameric building block of the HIV capsid","volume":"137","author":"Pornillos","year":"2009","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nature12162","article-title":"Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics","volume":"497","author":"Zhao","year":"2013","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nature09640","article-title":"Atomic-level modelling of the HIV capsid","volume":"469","author":"Pornillos","year":"2011","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S0022-2836(03)00289-4","article-title":"Antiviral inhibition of the HIV-1 capsid protein","volume":"327","author":"Tang","year":"2003","journal-title":"J. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jmb.2007.07.070","article-title":"Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein","volume":"373","author":"Kelly","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bmcl.2010.10.131","article-title":"Discovery of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly","volume":"21","author":"Fader","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1016\/j.bmcl.2013.03.074","article-title":"Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 2: Structure-activity relationships (SAR) of the C3-phenyl moiety","volume":"23","author":"Fader","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6643","DOI":"10.1128\/JVI.00493-12","article-title":"Distinct effects of two HIV-1 capsid assembly inhibitor families that bind the same site within the N-terminal domain of the viral CA protein","volume":"86","author":"Lemke","year":"2012","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1021\/acs.jmedchem.0c00015","article-title":"Design, synthesis, and mechanism study of benzenesulfonamide-containing phenylalanine derivatives as novel HIV-1 capsid inhibitors with improved antiviral activities","volume":"63","author":"Sun","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/s41586-020-2443-1","article-title":"Clinical targeting of HIV capsid protein with a long-acting small molecule","volume":"584","author":"Link","year":"2020","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Blair, W.S., Pickford, C., Irving, S.L., Brown, D.G., Anderson, M., Bazin, R., Cao, J., Ciaramella, G., Isaacson, J., and Jackson, L. (2010). HIV capsid is a tractable target for small molecule therapeutic intervention. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001220"},{"key":"ref_20","first-page":"1070","article-title":"Exploring modifications of an HIV-1 capsid inhibitor: Design, synthesis, and mechanism of action","volume":"5","author":"Xu","year":"2018","journal-title":"J. Drug Des. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1021\/acs.jmedchem.0c01810","article-title":"Rapid optimization of the metabolic stability of a human immunodeficiency virus type-1 capsid inhibitor using a multistep computational workflow","volume":"64","author":"Meuser","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vernekar, S.K.V., Sahani, R.L., Casey, M.C., Kankanala, J., Wang, L., Kirby, K.A., Du, H., Zhang, H., Tedbury, P.R., and Xie, J. (2020). Toward structurally novel and metabolically stable HIV-1 capsid-targeting small molecules. Viruses, 12.","DOI":"10.3390\/v12040452"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1093\/jac\/dkaa060","article-title":"Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients","volume":"75","author":"Marcelin","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112427","DOI":"10.1016\/j.ejmech.2020.112427","article-title":"Chemical profiling of HIV-1 capsid-targeting antiviral PF74","volume":"200","author":"Wang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","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":"ref_26","doi-asserted-by":"crossref","first-page":"18625","DOI":"10.1073\/pnas.1419945112","article-title":"Structural basis of HIV-1 capsid recognition by PF74 and CPSF6","volume":"111","author":"Bhattacharya","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1126\/science.abb4808","article-title":"Structural and mechanistic bases for a potent HIV-1 capsid inhibitor","volume":"370","author":"Bester","year":"2020","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28961","DOI":"10.1039\/C9RA05869A","article-title":"Discovery of novel 1,4-disubstituted 1,2,3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors","volume":"9","author":"Jiang","year":"2019","journal-title":"RSC Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.apsb.2020.07.016","article-title":"Novel PF74-like small molecules targeting the HIV-1 capsid protein: Balance of potency and metabolic stability","volume":"11","author":"Wang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112085","DOI":"10.1016\/j.ejmech.2020.112085","article-title":"Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities","volume":"190","author":"Sun","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.drudis.2013.08.014","article-title":"Chemistry-enabled drug delivery (prodrugs): Recent progress and challenges","volume":"19","author":"Clas","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1039\/C5OB02539G","article-title":"An approach to \u201cescape from flatland\u201d: Chemo-enzymatic synthesis and biological profiling of a library of bridged bicyclic compounds","volume":"14","author":"Franke","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1080\/17460441.2019.1653849","article-title":"Fragment-based screening with natural products for novel anti-parasitic disease drug discovery","volume":"14","author":"Liu","year":"2019","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"113051","DOI":"10.1016\/j.ejmech.2020.113051","article-title":"Exploiting the tolerant region I of the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding pocket. Part 2: Discovery of diarylpyrimidine derivatives as potent HIV-1 NNRTIs with high Fsp(3) values and favorable drug-like properties","volume":"213","author":"Jiang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1021\/jm901241e","article-title":"Escape from flatland: Increasing saturation as an approach to improving clinical success","volume":"52","author":"Lovering","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1021\/ci025590u","article-title":"Prediction of aqueous solubility of organic compounds based on a 3D structure representation","volume":"43","author":"Yan","year":"2003","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1002\/1521-3773(20000915)39:18<3168::AID-ANIE3168>3.0.CO;2-U","article-title":"Multicomponent reactions with isocyanides","volume":"39","author":"Ugi","year":"2000","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1021\/acsomega.9b03684","article-title":"Review on the Ugi multicomponent reaction mechanism and the use of fluorescent derivatives as functional chromophores","volume":"5","author":"Rocha","year":"2020","journal-title":"ACS Omega"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/COH.0000000000000472","article-title":"Inhibitors of the HIV-1 capsid, a target of opportunity","volume":"13","author":"Carnes","year":"2018","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.bmcl.2015.12.087","article-title":"Identification of a small molecule HIV-1 inhibitor that targets the capsid hexamer","volume":"26","author":"Xu","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ab.2006.08.005","article-title":"Exploring \u201cone-shot\u201d kinetics and small molecule analysis using the ProteOn XPR36 array biosensor","volume":"358","author":"Bravman","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jiang, X., Sharma, P.P., Rathi, B., Ji, X., Hu, L., Gao, Z., Kang, D., Wang, Z., Xie, M., and Xu, S. (2022). Discovery of novel 1,2,4-triazole phenylalanine derivatives targeting an unexplored region within the interprotomer pocket of the HIV capsid protein. J. Med. Virol., ahead of print.","DOI":"10.1002\/jmv.28064"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.3389\/fmicb.2017.01082","article-title":"Comparison of biochemical properties of HIV-1 and HIV-2 capsid proteins","volume":"8","author":"Miyazaki","year":"2017","journal-title":"Front. Microbiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/18\/5995\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:31:25Z","timestamp":1760142685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/18\/5995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,14]]},"references-count":43,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["molecules27185995"],"URL":"https:\/\/doi.org\/10.3390\/molecules27185995","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,14]]}}}