Pentacyclic compounds useful as inhibitors of hepatitis C virus NS3 helicase
Pentacyclic compounds useful as inhibitors of hepatitis C virus NS3 helicase
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可用作丙型肝炎病毒NS3解旋酶抑制剂的五环化合物
DOI：
10.1517/13543776.10.11.1777
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发表时间：
2000
影响因子：
6.6
通讯作者：
F. Schmitz
中科院分区：
文献类型：
--
作者：
L. Arabshahi;F. Schmitz
Vertex PharmPharmticals报道了一系列2，3，5-三取代-1，2，4-噻二唑-2-阳离子盐对丙型肝炎病毒(HCV)的多功能蛋白NS3具有抑制作用。NS3是一种多功能蛋白(丝氨酸蛋白酶和NTPase/解旋酶)，是非甲、非乙肝的病原体。通过简单的合成步骤制备了这些化合物，并在体外测定了它们对NS3不同酶活性的抑制特性，如解旋试验、分光光度法和高效液相ATPase活性测定。其中一些化合物在体外表现出低微摩尔范围的抑制活性，这使它们成为开发更有效的丙型肝炎病毒解旋酶抑制剂的有趣线索。没有提供活体数据。
A series of 2,3,5-trisubstituted-1,2,4-thiadiazol-2-ium salts is reported by Vertex Pharmaceuticals to possess inhibitory properties against NS3, a multifunctional (serine protease and NTPase/helicase) protein of hepatitis C virus (HCV), the causative agent of non-A, non-B hepatitis. These compounds were prepared by simple synthetic procedures and assayed in vitro for their inhibitory properties of different enzymatic activity of NS3, such as the unwinding assay, the spectrophotometric ATPase assay, as well as the HPLC ATPase activity assay. Some of them showed in vitro inhibitory activity in the low micromolar range, making them interesting leads for the development of more efficient HCV helicase inhibitors. No in vivo data are presented.