Synthesis and in vitro anti-hepatitis B and C virus activities of ring-expanded ('fat') nucleobase analogues containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system.
Synthesis and in vitro anti-hepatitis B and C virus activities of ring-expanded ('fat') nucleobase analogues containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system.
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含有咪唑并[4,5-e][1,3]二氮杂-4,8-二酮环系统的扩环（“脂肪”）核碱基类似物的合成及其体外抗乙型和丙型肝炎病毒活性。
DOI：
10.1016/j.bmcl.2005.09.015
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Hosmane,RamachandraS
中科院分区：
文献类型：
--
作者：
Zhang,Peng;Zhang,Ning;Korba,BrentE;Hosmane,RamachandraS
作为我们结构-活性关系研究的一部分，我们在此报告了许多含有咪唑并[4,5-e][1,3]二氮杂-4,8-二酮环系统的扩环（“脂肪”）核碱基的合成及其体外抗HBV和抗HCV活性。其中一种化合物 ZP-88 通过抑制培养的人肝母细胞瘤中细胞外病毒颗粒释放（EC50=1.7μM，CC50=286μM，SI=168）和细胞内 HBV 复制中间体（EC50=8.4μM，CC50=286μM，SI=34）的合成，表现出良好的抗 HBV 活性/毒性。 2.2.15 细胞。相比之下，大多数针对 HCV 测试的化合物仅具有边际活性/毒性特征，尽管这仍然优于参考化合物利巴韦林。
As part of our structure–activity relationship studies, we report here the synthesis and in vitro anti-HBV and anti-HCV activities of a number of ring-expanded (‘fat’) nucleobases containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system. One of the compounds, ZP-88, exhibited a good activity/toxicity profile against HBV by inhibition of the synthesis of extracellular virion release (EC50=1.7μM, CC50=286μM, SI=168) and intracellular HBV replication intermediates (EC50=8.4μM, CC50=286μM, SI=34) in cultured human hepatoblastoma 2.2.15 cells. By contrast, most of the compounds tested against HCV had only marginal activity/toxicity profile, although that was still better than that of the reference compound ribavirin.