Synthesis and in vitro activity evaluation of 2',3'-C-dimethyl carbocyclic nucleoside analogues as potential anti-HCV agents.
The first synthetic route of novel 2'(beta),3'(beta)-C-dimethyl carbodine analogues is described. The key intermediate cyclopentenyl alcohol 11(beta) prepared from Weinreb amide 4 via ring-closing metathesis (RCM) and vicinal dihydroxylation. Coupling of 12 with nucleosidic bases via the Pd(0) catalyzed reaction followed by stereoselective dihydoxylation and deprotection afforded the target carbocyclic nucleoside analogues. The synthesized compounds were evaluated as inhibitors of the hepatitis C virus (HCV) in Huh-7 cell line in vitro. However, the nucleosides failed to inhibit HCV RNA replication in the cell-based replicon assay (EC(50) > microM).
Ko
Ok Hyun
OH
BK21-Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
Hong
Joon Hee
JH
D000146:Acids, Carbocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D003562:Cytidine; C033357:carbodine