Exploration of the effects of linker chain modifications on anti-HIV activities in a series of cosalane analogues.
Exploration of the effects of linker chain modifications on anti-HIV activities in a series of cosalane analogues.
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DOI：
10.1016/0968-0896(96)00159-9
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发表时间：
1996-10
影响因子：
3.5
通讯作者：
W. Gołębiewski;R. Keyes;M. Cushman
中科院分区：
文献类型：
--
作者：
W. Gołębiewski;R. Keyes;M. Cushman
研究了一系列柯柳烷类似物中连接链修饰的影响。研究的修饰包括：（1）将二氯二异丙基甲烷和胆甾烷部分之间的三碳连接链缩短一个碳原子;（2）将连接链延长一个碳原子;（3）将连接链中的双键氢化;（4）将连接链的连接点从C-3改变为C-6;（5）将连接链的连接点从C-6改变为C-6。（5）在类固醇和接头链之间插入磷酸酯。除了磷酸修饰（其消除了抗HIV活性并增加了细胞毒性）之外，连接链修饰在抗HIV效力方面产生了相对较小的变化。因此，类固醇和连接的连接体链的cosalane似乎只提供一个一般的亲脂性附件的二氯二异丙基甲烷药效团。
The effects of linker chain modifications were investigated in a series of cosalane analogues. The modifications investigated included: (1) shortening the three-carbon linker chain between the dichlorodisalicylmethane and the cholestane moiety by one carbon atom; (2) lengthening the linker chain by one carbon; (3) hydrogenation of the double bond in the linker chain; (4) changing the point of attachment of the linker chain from C-3 to C-6; (5) insertion of a phosphate between the steroid and the linker chain. With the exception of the phosphate modification, which abolished anti-HIV activity and increased cytotoxicity, the linker chain modifications produced relatively minor changes in anti-HIV potency. The steroid and attached linker chain of cosalane therefore appear only to provide a general lipophilic appendage for the dichlorodisalicylmethane pharmacophore.