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Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound <jats:bold>P\u20102<\/jats:bold>, which possessed a superior potency to the lead compound <jats:bold>DB02<\/jats:bold> against wild\u2010type HIV\u20101 and a variety of HIV\u2010resistant mutant viruses significantly. Furthermore, the water solubility of <jats:bold>P\u20102<\/jats:bold> was nearly 17 times higher than that of <jats:bold>DB02<\/jats:bold>, and the pharmacokinetic test in rats showed that <jats:bold>P\u20102<\/jats:bold> demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the <jats:italic>C<\/jats:italic>\u20102 side chain of <jats:bold>DB02<\/jats:bold> was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of <jats:italic>S<\/jats:italic>\u2010DACOs type of NNRTIs.<\/jats:p>","DOI":"10.1002\/ddr.22036","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:44:12Z","timestamp":1675827852000},"page":"465-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and anti\u2010HIV activity of non\u2010nucleoside reverse\u2010transcriptase inhibitor DB02 phosphate derivatives based on water\u2010soluble 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