Golebiewski W M, Keyes R F, Cushman M
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Bioorg Med Chem. 1996 Oct;4(10):1637-48. doi: 10.1016/0968-0896(96)00159-9.
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 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.
在一系列科萨烷类似物中研究了连接链修饰的效果。所研究的修饰包括：（1）将二氯二水杨基甲烷与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）连接链中双键的氢化；（4）将连接链的连接点从C-3改为C-6；（5）在类固醇和连接链之间插入一个磷酸酯。除了磷酸酯修饰消除了抗HIV活性并增加了细胞毒性外，连接链修饰在抗HIV活性方面产生了相对较小的变化，并且增加了细胞毒性，连接链修饰在抗HIV效力方面产生了相对较小的变化。因此，科萨烷的类固醇和连接链似乎只为二氯二水杨基甲烷药效基团提供了一个一般的亲脂性附属物。
