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

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journal contribution
posted on 08.01.2009, 00:00 by Hyo-Joong Kim, Ashoke Sharon, Chandralata Bal, Jianing Wang, Madhan Allu, Zhuhui Huang, Michael G. Murray, Leda Bassit, Raymond F. Schinazi, Brent Korba, Chung K. Chu
A series of 7-deazaneplanocin A (7-DNPA, 2) analogues were synthesized and evaluated for in vitro antiviral activity against HBV and HCV. The syntheses 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, 1315, 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 = 0.3−3.3 μM). In addition, compound 24 also showed activity against lamivudine- and adefovir-associated HBV mutants.