发现具有抑制 HIV-1 复制活性的 3,4-二氢嘧啶-2(1H)-酮。

Discovery of 3,4-dihydropyrimidin-2(1H)-ones with inhibitory activity against HIV-1 replication.

机构信息

Medicinal Chemistry Group, Institut Pasteur Korea (IP-K), Sampyeong-dong 696, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.

出版信息

Bioorg Med Chem Lett. 2012 Mar 1;22(5):2119-24. doi: 10.1016/j.bmcl.2011.12.090. Epub 2012 Jan 12.

DOI:10.1016/j.bmcl.2011.12.090

Abstract

3,4-Dihydropyrimidin-2(1H)-ones (DHPMs) were selected and derivatized through a HIV-1 replication assay based on GFP reporter cells. Compounds 14, 25, 31, and 36 exhibited significant inhibition of HIV-1 replication with a good safety profile. Chiral separation of each enantiomer by fractional crystallization showed that only the S enantiomer retained anti-HIV activity. Compound (S)-40, a novel and potent DHPM analog, could serve as an advanced lead for further development and the determination of the mechanism of action.

摘要

3,4-二氢嘧啶-2(1H)-酮类化合物（DHPMs）通过基于 GFP 报告细胞的 HIV-1 复制试验进行选择和衍生化。化合物 14、25、31 和 36 对 HIV-1 复制具有显著的抑制作用，且安全性良好。通过分步结晶对每个对映异构体进行手性分离表明，只有 S 对映异构体保留抗 HIV 活性。新型强效 DHPM 类似物（S）-40 可作为进一步开发和确定作用机制的先导化合物。

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