{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:10:19Z","timestamp":1787170219626,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273773"],"award-info":[{"award-number":["82273773"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973181"],"award-info":[{"award-number":["81973181"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Non\u2010nucleoside reverse transcriptase inhibitors (NNRTIs) are an important component of anti\u2010acquired immunodeficiency syndrome treatment regimen. In the present work, with the previously reported compound\n                    <jats:bold>K\u201016c<\/jats:bold>\n                    as lead, a series of novel 2,4,5\u2010trisubstituted pyrimidine derivatives were designed based on the cocrystal structure of\n                    <jats:bold>K\u201016c<\/jats:bold>\n                    \/RT, with the aim to improve the anti\u2010human immunodeficiency virus type\u20101 (HIV\u20101)\u00a0activities and metabolic stability properties. Compound\n                    <jats:bold>11b1<\/jats:bold>\n                    exhibited the most potent antiviral activity against wild\u2010type (WT) and a panel of single mutant HIV\u20101 strains (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20092.4\u221212.4\u2009nM), being superior to or comparable to those of the approved drug etravirine. Meanwhile,\n                    <jats:bold>11b1<\/jats:bold>\n                    exhibited moderate cytotoxicity (CC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20094.96\u2009\u03bcM) and high selectivity index (SI\u2009=\u20091189) toward HIV\u20101\u00a0WT\u00a0strain. As for HIV\u20101 RT inhibition test,\n                    <jats:bold>11b1<\/jats:bold>\n                    possessed excellent inhibitory potency (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.04\u2009\u03bcM) and confirmed its target was RT. Moreover, the molecular dynamics simulation was performed to elucidate the improved drug resistance profiles. Moreover,\n                    <jats:bold>11b1<\/jats:bold>\n                    was demonstrated with favorable safety profiles and pharmacokinetic properties in vivo, indicating that\n                    <jats:bold>11b1<\/jats:bold>\n                    is a potential anti\u2010HIV\u20101 drug candidate worthy of further development.\n                  <\/jats:p>","DOI":"10.1002\/jmv.29502","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T06:57:29Z","timestamp":1709794649000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structure\u2010based design of diarylpyrimidines and triarylpyrimidines as potent HIV\u20101 NNRTIs with improved metabolic stability and drug resistance profiles"],"prefix":"10.1002","volume":"96","author":[{"given":"Minghui","family":"Xie","sequence":"first","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China"},{"name":"China\u2010Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongji","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"De Clercq","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy Rega Institute for Medical Research, K. 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