Synthesis and anti-hepatitis C virus activity of 2'(beta)-hydroxyethyl and 4'(alpha)-hydroxymethyl carbodine analogues.
2'(beta)-Hydroxyethylated adenosine is a potent and selective inhibitor of hepatitis C virus (HCV) replication targeting the RNA-dependent RNA polymerase of HCV, NS5B. The synthesis and anti-HCV evaluation of carbodine analogues are described. The cyclopentene intermediate 10 was successfully made via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis. Coupling of bases via a Pd(0) catalyst, selective dihydroxylation, and desilylation yielded the target carbodine analogues. Cytosine analogue 17 weakly inhibited the replication of the HCV replicon in Hua-7 cells by 50% at 21.1 muM.
Liu
Lian Jin
LJ
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* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; 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
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D009705:Nucleosides; D003562:Cytidine; C033357:carbodine