Synthesis of Carbocyclic Formycin Analogues as Antiviral Agents

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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.