Synthesis and antiviral evaluation of 9-(S)-[3-alkoxy-2-(phosphonomethoxy)propyl]nucleoside alkoxyalkyl esters: inhibitors of hepatitis C virus and HIV-1 replication.
Synthesis and antiviral evaluation of 9-(S)-[3-alkoxy-2-(phosphonomethoxy)propyl]nucleoside alkoxyalkyl esters: inhibitors of hepatitis C virus and HIV-1 replication.
复制标题
9-(S)-[3-烷氧基-2-(膦酰甲氧基)丙基]核苷烷氧基烷基酯的合成和抗病毒评价：丙型肝炎病毒和HIV-1复制的抑制剂。
DOI：
10.1016/j.bmc.2011.06.009
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发表时间：
2011
影响因子：
3.5
通讯作者：
Hostetler,KarlY
中科院分区：
文献类型：
--
作者：
Valiaeva,Nadejda;Wyles,DavidL;Schooley,RobertT;Hwu,JuliaB;Beadle,JamesR;Prichard,MarkN;Hostetler,KarlY
We reported previously that octadecyloxyethyl 9-(S)-[3-hydroxy-2-(phosphonomethoxy)-propyl]adenine (ODE-(S)-HPMPA) was active against genotype 1b and 2a hepatitis C virus (HCV) replicons. This is surprising because acyclic nucleoside phosphonates have been regarded as having antiviral activity only against double stranded DNA viruses, HIV and HBV. We synthesized octadecyloxyethyl 9-(S)-[3-methoxy-2-(phosphonomethoxy)propyl]-adenine and found it to be active in genotype 1b and 2a HCV replicons with EC50values of 1–2μM and a CC50of >150μM. Analogs with substitutions at the 3′-hydroxyl larger than methyl or ethyl, or with other purine bases were less active but most compounds had significant antiviral activity against HIV-1 in vitro. The most active anti-HIV compound was octadecyloxyethyl 9-(R)-[3-methoxy-2-(phosphonomethoxy)propyl]guanine with an EC50<0.01 nanomolar and a selectivity index of >4.4million.
