Synthesis of Carbocyclic Formycin Analogues as Antiviral Agents

描述（由申请人提供）：本研究的主要目的是合成和表征可用于病毒性传染病治疗的碳环核苷，特别是乙型肝炎（HBV）和丙型肝炎（HCV）。我们计划合成一类新的核苷，并研究它们的抗病毒特性，以发现具有更高效力、更低细胞毒性和更大代谢稳定性的类似物。具体来说，我们的目标是合成一些天然存在的核苷，福霉素的碳环类似物。所提出的化合物被设计成系统地结合两类已知抗病毒化合物的结构特征。目标化合物将通过标准分离技术合成和纯化，然后使用核磁共振（NMR）和傅立叶变换红外光谱等光谱技术对其进行表征。将对目标化合物进行抗病毒试验，以研究其对乙型和丙型肝炎病毒的活性。在未来的项目中，将对目标化合物和更多类似物进行测试，以确定它们对多种病毒的生物活性。病毒性传染病（包括乙型肝炎和丙型肝炎）是公共卫生领域中存在重大健康差异的领域之一。当前治疗干预措施的严重局限性要求开发新的药物。本提案旨在通过合成一类新的碳环核苷作为抗病毒药物来解决这一需求。碳环核苷在治疗病毒性传染病，如人类免疫缺陷病毒（艾滋病毒、艾滋病）、乙型肝炎病毒和疱疹病毒方面的应用越来越广泛。

DESCRIPTION (provided by applicant): The main objective of this research is to synthesize and characterize carbocyclic nucleosides that can be used in the treatment of viral infectious diseases, specifically hepatitis B (HBV) and hepatitis C (HCV). We plan to synthesize a novel class of nucleosides and investigate their antiviral properties in an effort to discover analogs with increased potency, reduced cytotoxicity, and greater metabolic stability. Specifically, we aim to synthesize a number of carbocyclic analogs of a naturally occurring nucleoside, formycin. The proposed compounds are designed to systematically combine structural features of two known classes of antiviral compounds. The target compounds will be synthesized and purified by standard separation techniques and then characterized by using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared spectroscopy etc. Antiviral assays of the target compounds will be conducted to investigate their activity against hepatitis B and hepatitis C viruses. In future projects, the target compounds and many more analogs will be tested to determine their biological activities against a wide range of viruses. Project Narrative/Relevance Viral infectious diseases (including Hepatitis B and Hepatitis C) are one of the areas of public health where significant health disparity is seen. The serious limitations of the current therapeutic interventions call for the development of new agents. This proposal is designed to address this need by synthesizing a new class of carbocyclic nucleosides as antiviral agents. Carbocyclic nucleosides are finding increased application in the treatment of viral infectious diseases such as Human Immunodeficiency Virus (HIV, AIDS), Hepatitis B virus and the Herpes viruses.