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优化二芳基嗪类化合物作为抗 HIV 药物，显著提高其溶解度。

Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility.

机构信息

Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.

出版信息

Bioorg Med Chem Lett. 2013 Sep 15;23(18):5213-6. doi: 10.1016/j.bmcl.2013.06.091. Epub 2013 Jul 8.

DOI:10.1016/j.bmcl.2013.06.091
PMID:23937980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3759246/
Abstract

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are reported that have ca. 100-fold greater solubility than the structurally related drugs etravirine and rilpivirine, while retaining high anti-viral activity. The solubility enhancements come from strategic placement of a morpholinylalkoxy substituent in the entrance channel of the NNRTI binding site. Compound 4d shows low-nanomolar activity similar to etravirine towards wild-type HIV-1 and key viral variants.

摘要

报道了一种新型 HIV-1 逆转录酶非核苷抑制剂，其水溶性比结构相关药物依曲韦林和利匹韦林高约 100 倍，同时保持了高抗病毒活性。这种水溶性的提高是通过在 NNRTI 结合部位的入口通道中巧妙地引入吗啉基烷氧基取代基实现的。化合物 4d 对野生型 HIV-1 和关键病毒变异株的活性与依曲韦林相似，均为低纳摩尔级。

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本文引用的文献

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Treatment of HIV infection with once-daily regimens.每日一次方案治疗 HIV 感染。
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Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase inhibitors.优化 2,4-二芳基苯胺作为非核苷 HIV-1 逆转录酶抑制剂。
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Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase.通过向 HIV-1 逆转录酶入口通道扩展发现二聚抑制剂。
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