Synthesis Anti-Hepatitis B Virus and Anti-Hepatitis C Virus Activities of 7-Deazaneplanocin A Analogues In Vitro

摘要

A series of 7-deazaneplanocin A (7-DNPA, >2) analogues were synthesized and evaluated for in vitro antiviral activity against HBV and HCV. The synthesis of target carbocyclic nucleosides were accomplished via a convergent procedure. 7-Substitutions were introduced by using 7-substituted-7-deaza heterocyclic base precursors (F, Cl, Br, and I) or via substitution reactions after the synthesis of the carbocyclic nucleosides. Among the synthesized compounds, >2, 13–15, 24 and >27 exhibited significant anti-HCV activity (EC50 ranged from 1.8 to 20.1 µM), and compounds >2, 15, 22 and >24 demonstrated moderate to potent anti-HBV activity (EC50 0.3 to 3.3 µM). In addition, the compound >24 also showed the activity against lamivudine- and adefovir- associated HBV mutants.