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Design, synthesis, and biological evaluation of novel 2′-deoxy-2′-fluoro-2′-C-methyl 8-azanebularine derivatives as potent anti-HBV agents.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jun2019, Vol. 29 Issue 11, p1291-1297. 7p. - Publication Year :
- 2019
-
Abstract
- This work describes the synthesis of new 2′-fluoro-2′- C -methyl 8-azanebularine nucleoside derivatives with moderate to good in vitro anti-HBV activity. 2g can efficiently inhibit the wild-type and lamivudine-resistant HBV DNA replication. Hepatitis B virus (HBV) is a global health problem requiring more efficient and better tolerated anti-HBV agent. In this paper, a series of novel 2′-deoxy-2′-fluoro-2′- C -methyl-β- d -arabinofuranosyl 8-azanebularine analogues (1 and 2a) and N4 -substituted 8-azaadenosine derivatives (2b-g) were designed, synthesized and screened for in vitro anti-HBV activity. Two concise and practical synthetic routes were developed toward the structural motif construction of 2′-deoxy-2′-fluoro-2′- C -methyl-β- d -arabinofuranosyl 8-azainosine from the ribonolactone 3 under mild conditions. The in vitro anti-HBV screening results showed that these 8-azanebularine analogues had a significant inhibitory effect on the expression of HBV antigens and HBV DNA at a concentration of 20 μM. Among them, halogen-substituted 8-azaadenosine derivative 2g displayed activities comparable to that of 3TC. In particular, 2g retained excellent activity against lamivudine-resistant HBV mutants. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 29
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 136071539
- Full Text :
- https://doi.org/10.1016/j.bmcl.2019.04.005