{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T06:52:14Z","timestamp":1775371934924,"version":"3.50.1"},"reference-count":28,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p> A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC<jats:sub>50<\/jats:sub>) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC<jats:sub>50<\/jats:sub> value of 10 nM and a high selectivity index of 1923. Preliminary structure\u2013activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The excellent activity of 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC<jats:sub>50<\/jats:sub>: 0.010\u2009\u00b1\u20090.006\u2009\u00b5M, SI: &gt;1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants. <\/jats:p><\/jats:sec>","DOI":"10.1177\/2040206614566584","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T17:01:37Z","timestamp":1426525297000},"page":"3-18","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and <i>N<\/i>-3,5-dimethylbenzyl-substituted urea derivatives"],"prefix":"10.1177","volume":"24","author":[{"given":"Norikazu","family":"Sakakibara","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Kagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Baba","sequence":"additional","affiliation":[{"name":"Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mika","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Toyama","sequence":"additional","affiliation":[{"name":"Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Demizu","sequence":"additional","affiliation":[{"name":"Division of Organic Chemistry, National Institute of Health Sciences, Setagaya, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Misawa","sequence":"additional","affiliation":[{"name":"Division of Organic Chemistry, National Institute of Health Sciences, Setagaya, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Division of Organic Chemistry, National Institute of Health Sciences, Setagaya, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohji","family":"Irie","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Kagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihisa","family":"Kato","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Kagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tokumi","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Kagawa, 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