title: Synthesis and antiviral activity of cyclopropyl-spirocarbocyclic adenosine, (4R,5S,6R,7R)-4-(6-amino-9H-purin-9-yl)-7-(hydroxymethyl)spiro[2.4]heptane-5,6-diol against hepatitis C virus.
abstract: An efficient method was developed for the synthesis of 6-exocyclic methylene carbocyclic intermediate 4. The Simmons-Smith cyclopropanation protocol was applied on the 6-exocyclic methylene of intermediate 4 and demonstrated its utility for the synthesis of novel class of a spiro-carbocyclic nucleoside analog 8. The titled compound 8 demonstrated a significant antiviral activity against HCV with EC(50) values of 0.273 and 0.368 μM in genotypes 1A and 1B, respectively.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Gadthula
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Rawal
authors.forename: Ashoke
authors.initials: A
authors.lastname: Sharon
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.forename: Brent
authors.initials: B
authors.lastname: Korba
authors.forename: Chung K
authors.initials: CK
authors.lastname: Chu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D016174:Hepacivirus / Q000187:drug effects*; D006536:Heptanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C562363:4-(6-amino-9H-purin-9-yl)-7-(hydroxymethyl)spiro(2.4)heptane-5,6-diol; D000998:Antiviral Agents; D006536:Heptanes; D013141:Spiro Compounds; D000241:Adenosine