Synthesis and anti-HCV evaluation of 4'(alpha)-ethyl and 2'(beta)-methyl-carbodine analogues.
Novel 4'(alpha)-ethyl-2'(beta)-methyl carbocyclic nucleoside analogues have been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell culture. The construction of cyclopentene intermediate 12 beta was successfully made via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis (RCM) starting from Weinreb amide 5. Selective dihydroxylation and desilylation gave the target carbodine analogues. The synthesized nucleoside analogues mentioned above 18 and 19 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line (LucNeo#2). However, the synthesized nucleosides neither showed any significant antiviral activity nor toxicity up to 50 microM.
Li
Hua
H
BK21-Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
Yoo
Jin Cheol
JC
Hong
Joon Hee
JH
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003517:Cyclopentanes / Q000138:chemical synthesis; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D019384:Nucleic Acid Synthesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D003517:Cyclopentanes; D019384:Nucleic Acid Synthesis Inhibitors; D003562:Cytidine; C033357:carbodine