Synthesis and Anti-Hepatitis B Virus and Anti-Hepatitis C Virus Activities of 7-Deazaneplanocin A Analogues in Vitro
journal contributionposted 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, 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 = 0.3−3.3 μM). In addition, compound 24 also showed activity against lamivudine- and adefovir-associated HBV mutants.