{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:57:17Z","timestamp":1760317037930,"version":"build-2065373602"},"reference-count":29,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T00:00:00Z","timestamp":1473984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Japanese Ministry of Health, Labor, and Welfare","award":["H18-AIDS-Wakate-003"],"award-info":[{"award-number":["H18-AIDS-Wakate-003"]}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2016,10,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A novel HIV\u20101 inhibitor, 6\u2010(<jats:italic>tert<\/jats:italic>\u2010butyl)\u20104\u2010phenyl\u20104\u2010(trifluoromethyl)\u20101<jats:italic>H<\/jats:italic>,3<jats:italic>H<\/jats:italic>\u20101,3,5\u2010triazin\u20102\u2010one (compound <jats:bold>1<\/jats:bold>), was identified from a compound library screened for the ability to inhibit HIV\u20101 replication. EC<jats:sub>50<\/jats:sub> values of compound <jats:bold>1<\/jats:bold> were found to range from 107.9 to 145.4\u2005n<jats:sc>m<\/jats:sc> against primary HIV\u20101 clinical isolates. In in\u2005vitro assays, HIV\u20101 reverse transcriptase (RT) activity was inhibited by compound <jats:bold>1<\/jats:bold> with an EC<jats:sub>50<\/jats:sub> of 4.3\u2005\u03bc<jats:sc>m<\/jats:sc>. An assay for resistance to compound <jats:bold>1<\/jats:bold> selected a variant of HIV\u20101 with a RT mutation (RT<jats:sup>L100I<\/jats:sup>); this frequently identified mutation confers mild resistance to non\u2010nucleoside RT inhibitors (NNRTIs). A recombinant HIV\u20101 bearing RT<jats:sup>L100I<\/jats:sup> exhibited a 41\u2010fold greater resistance to compound <jats:bold>1<\/jats:bold> than the wild\u2010type virus. Compound <jats:bold>1<\/jats:bold> was also effective against HIV\u20101 with RT<jats:sup>K103N<\/jats:sup>, one of the major mutations that confers substantial resistance to NNRTIs. Computer\u2010assisted docking simulations indicated that compound <jats:bold>1<\/jats:bold> binds to the RT NNRTI binding pocket in a manner similar to that of efavirenz; however, the putative compound <jats:bold>1<\/jats:bold> binding site is located further from RT<jats:sup>K103<\/jats:sup> than that of efavirenz. Compound <jats:bold>1<\/jats:bold> is a novel NNRTI with a unique drug\u2010resistance profile.<\/jats:p>","DOI":"10.1002\/cmdc.201600375","type":"journal-article","created":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T05:29:39Z","timestamp":1474003779000},"page":"2320-2326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Triazinone Derivative Inhibits HIV\u20101 Replication by Interfering with Reverse Transcriptase Activity"],"prefix":"10.1002","volume":"11","author":[{"given":"Emiko","family":"Urano","sequence":"first","affiliation":[{"name":"AIDS Research Center National Institute of Infectious Diseases  1-23-1 Toyama Shinjuku-ku Tokyo 162-8640 Japan"},{"name":"The Virus\u2013Cell Interaction Section HIV Dynamics and Replication Program National Cancer Institute  Frederick MD 21701 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Miyauchi","sequence":"additional","affiliation":[{"name":"AIDS Research Center National Institute of Infectious Diseases  1-23-1 Toyama Shinjuku-ku Tokyo 162-8640 Japan"},{"name":"RIKEN Center for Integrative Medical Sciences RIKEN Yokohama Institute  1-7-22 Suehiro-cho, Tsurumi Yokohama Kanagawa 230-0045 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Osaka Prefectural Institute of Public Health  3-69, Nakamachi, 1-chome Higashinari-ku Osaka 537-0025 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Hamatake","sequence":"additional","affiliation":[{"name":"AIDS Research Center National Institute of Infectious Diseases  1-23-1 Toyama Shinjuku-ku Tokyo 162-8640 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherimay D.","family":"Ablan","sequence":"additional","affiliation":[{"name":"The Virus\u2013Cell Interaction Section HIV Dynamics and Replication Program National Cancer Institute  Frederick MD 21701 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Fudo","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Chiba University  1-33 Yayoi-cho Inage-ku Chiba 263-8522 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric O.","family":"Freed","sequence":"additional","affiliation":[{"name":"The Virus\u2013Cell Interaction Section HIV Dynamics and Replication Program National Cancer Institute  Frederick MD 21701 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyuji","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Chiba University  1-33 Yayoi-cho Inage-ku Chiba 263-8522 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Komano","sequence":"additional","affiliation":[{"name":"AIDS Research Center National Institute of Infectious Diseases  1-23-1 Toyama Shinjuku-ku Tokyo 162-8640 Japan"},{"name":"Department of Infectious Diseases Osaka Prefectural Institute of Public Health  3-69, Nakamachi, 1-chome Higashinari-ku Osaka 537-0025 Japan"},{"name":"Department of Clinical Laboratory Nagoya Medical Center  4-1-1 Sannomaru Naka-ku Nagoya 460-0001 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,16]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e328331c478"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60676-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871526514666140321104049"},{"key":"e_1_2_6_4_1","first-page":"341","volume":"8","author":"Arribas J. 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