某些第二代亚甲基环丙基核苷的合成及抗病毒活性。
Synthesis and antiviral activity of certain second generation methylenecyclopropane nucleosides.
机构信息
Microbiotix, Inc., One Innovation Drive, Worcester, MA 01605, USA.
出版信息
Bioorg Med Chem. 2012 Jun 15;20(12):3710-8. doi: 10.1016/j.bmc.2012.04.049. Epub 2012 May 1.
Abstract
A second-generation series of substituted methylenecyclopropane nucleosides (MCPNs) has been synthesized and evaluated for antiviral activity against a panel of human herpesviruses, and for cytotoxicity. Although alkylated 2,6-diaminopurine analogs showed little antiviral activity, the compounds containing ether and thioether substituents at the 6-position of the purine did demonstrate potent and selective antiviral activity against several different human herpesviruses. In the 6-alkoxy series, antiviral activity depended on the length of the ether carbon chain, with the optimum chain length being about four carbon units long. For the corresponding thioethers, compounds containing secondary thioethers were more potent than those with primary thioethers.
摘要
已合成并评估了第二代取代亚甲基环丙烷核苷（MCPN）系列，以评估其针对人疱疹病毒的抗病毒活性和细胞毒性。尽管烷基化的 2,6-二氨基嘌呤类似物显示出很少的抗病毒活性，但在嘌呤的 6-位具有醚和硫醚取代基的化合物对几种不同的人疱疹病毒表现出强大且选择性的抗病毒活性。在 6-烷氧基系列中，抗病毒活性取决于醚碳链的长度，最佳链长约为四个碳原子。对于相应的硫醚，含仲硫醚的化合物比含伯硫醚的化合物更有效。
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