设计、合成及吲哚类化合物作为靶向 Gp41 的新型抑制剂的评价。
Design, synthesis, and evaluation of indole compounds as novel inhibitors targeting Gp41.
机构信息
Department of Basic Sciences, Touro University--California, 1310 Johnson Lane, Mare Island, Vallejo, CA 94592, United States.
出版信息
Bioorg Med Chem Lett. 2010 Mar 1;20(5):1500-3. doi: 10.1016/j.bmcl.2010.01.111. Epub 2010 Jan 25.
Abstract
A series of indole ring containing compounds were designed based on the structure of the gp41 complex in the region of the hydrophobic pocket. These compounds were synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence binding assay and cell-cell fusion assay. The observed inhibition constant of compound 7 was 2.1microM, and the IC(50) for cell-cell fusion inhibition was 1.1microM. Assay data indicated that 7 is a promising lead compound for optimization into an effective low molecular weight fusion inhibitor.
摘要
基于 gp41 疏水口袋区域的结构，设计了一系列含吲哚环的化合物。这些化合物通过 Suzuki 偶联反应进行合成，并通过荧光结合测定法和细胞-细胞融合测定法进行评估。化合物 7 的观察抑制常数为 2.1μM，细胞-细胞融合抑制的 IC50 为 1.1μM。测定数据表明，7 是一种很有前途的先导化合物，可优化为有效的低分子量融合抑制剂。
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