| Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization |
| Wang, JB; Ma, MD; Lu, N; Yang, YZ; Yang, JX; Li, YM; Xie, CQ; Ma, NY; Luo, RH; Wang, YP; Yang, LM; Zhang, HB; Zheng, YT; He, YP
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| 2023
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| 发表期刊 | DRUG DEVELOPMENT RESEARCH
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| ISSN | 0272-4391
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| 卷号 | 84期号:3页码:423-432 |
| 摘要 | To improve the water solubility of anti-human immunodeficiency virus (HIV) agent DB02, an excellent non-nucleoside reverse-transcriptase inhibitor (NNRTI) obtained in our previous efforts, we designed and synthesized four phosphate derivatives of DB02 based on the molecular model of DB02 with RT. Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound P-2, which possessed a superior potency to the lead compound DB02 against wild-type HIV-1 and a variety of HIV-resistant mutant viruses significantly. Furthermore, the water solubility of P-2 was nearly 17 times higher than that of DB02, and the pharmacokinetic test in rats showed that P-2 demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the C-2 side chain of DB02 was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of S-DACOs type of NNRTIs. |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13969
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| 专题 | 科研部门_分子免疫药理学（郑永唐）
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推荐引用方式
GB/T 7714 |
Wang, JB,Ma, MD,Lu, N,et al. Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization[J]. DRUG DEVELOPMENT RESEARCH,2023,84(3):423-432.
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| APA |
Wang, JB.,Ma, MD.,Lu, N.,Yang, YZ.,Yang, JX.,...&He, YP.(2023).Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization.DRUG DEVELOPMENT RESEARCH,84(3),423-432.
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| MLA |
Wang, JB,et al."Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization".DRUG DEVELOPMENT RESEARCH 84.3(2023):423-432.
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