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.
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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