Anti-AIDS Agents 90. Novel C-28 Modified Bevirimat Analogues as Potent HIV Maturation Inhibitors

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• 作者：Keduo Qian ; Ibrahim D. Bori ; Chin-Ho Chen ; Li Huang ; Kuo-Hsiung Lee
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：September 27, 2012
• 年：2012
• 卷：55
• 期：18
• 页码：8128-8136
• 全文大小：369K
• 年卷期：v.55,no.18(September 27, 2012)
• ISSN：1520-4804

文摘

In a continuing study of bevirimat (2), the anti-HIV-maturation clinical trials agent, 28 new betulinic acid (BA, 1) derivatives were designed and synthesized. Among these compounds, 17, with a C-28 MEM ester moiety, and 22, with a C-28 ethyl hexanoate, increased the anti-HIV replication activity compared with 2 by 2-fold while compounds 40, 41, 48, and 49, with C-28 piperazine or piperidine amide substitutions, increased the activity by 3- to 15-fold. The best new compound, 41, exhibited an anti-HIV IC₅₀ of 0.0059 渭M compared with 0.087 渭M for 2. All of the active compounds showed only antimaturation effects, as confirmed by TZM-bl assay, in blocking the HIV replication. The results suggest that proper C-28 substitutions can further enhance the antimaturation activity of 2 without any antientry effects. Thus, 41 may serve as a promising new lead for development of anti-AIDS clinical trial candidates.