Development of Inhibitors Against HCV Infection

描述(申请人提供)：丙型肝炎病毒感染最多 在美国常见的慢性血液传播感染。这里有大约 每年新增36,000名感染者，其中25%-30%是 有症状。据估计，390万美国人(1.8%)已经 被感染了。由丙型肝炎病毒感染引起的慢性肝病排在第十位 美国成年人的主要死因，占 约占所有死亡人数的1%。到目前为止，还没有有效的文化 可用于评价化合物的体外抗丙型肝炎病毒活性。至 克服这一困难，代用动物病毒正在被使用，包括 牛病毒性腹泻病毒、黄热病病毒、登革热病毒和班兹病毒。 我们已经确定了一种化合物(ZX-2401)，它显示出一种重要的抗病毒作用 对这些代理病毒的活性。此应用程序的总体范围 是为了研究这种化合物及其衍生物作为 潜在的丙型肝炎病毒抑制剂。这些新化合物的具体目标是 包括合成ZX-2401或拟议研究所需的衍生物， 丙型肝炎病毒复制子系统的体外抗病毒研究及其细胞毒性 检测，进行与干扰素-α联合的研究，并进行 行动机制研究。

DESCRIPTION (Provided by applicant): Hepatitis C viral infection is the most common chronic bloodborne infection in the United States. There are about 36,000 new infections every year, and 25-30 percent of those infections are symptomatic. It is estimated that 3.9 million (1.8 percent) Americans have been infected. Chronic liver disease, which is caused by HCV infection, is the tenth leading cause of death among adults in the United States, accounting for approximately 1 percent of all deaths. To date, there is no efficient culture system available to evaluate the activity of compounds against HCV in vitro. To overcome this difficulty, surrogate animal viruses are being used, including bovine viral diarrhea virus, yellow fever virus, dengue virus, and banzi virus. We have identified a compound (ZX-2401) that shows a significant antiviral activity against these surrogate viruses. The overall scope of this application is to investigate the feasibility of this compound and its derivatives as potential inhibitors of HCV. The specific aims for these novel compounds include synthesizing ZX-2401 or derivatives as needed for the proposed studies, performing in vitro antiviral studies in HCV replicon system and cytotoxicity testing, performing studies in combination with IFN-alpha, and performing mechanism of action studies.