Synthesis of 9-(2-beta-C-methyl-beta-d-ribofuranosyl)-6-substituted purine derivatives as inhibitors of HCV RNA replication.
A series of 9-(2'-beta-C-methyl-beta-d-ribofuranosyl)-6-substituted purine derivatives were synthesized as potential inhibitors of HCV RNA replication. Their inhibitory activities in a cell based HCV replicon assay were reported. A prodrug approach was used to further improve the potency of these compounds by increasing the intracellular levels of 5'-monophosphate metabolites. These nucleotide prodrugs showed much improved inhibitory activities of HCV RNA replication.
Ding
Yili
Y
Valeant Pharmaceuticals International, 3300 Hyland Avenue Costa Mesa, CA 92626, USA. yding@icnpharm.com
Girardet
Jean-Luc
JL
Hong
Zhi
Z
Lai
Vicky C H
VC
An
Haoyun
H
Koh
Yung-Hyo
YH
Shaw
Stephanie Z
SZ
Zhong
Weidong
W
D000998:Antiviral Agents / Q000138:chemical synthesis*; D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics; D012093:Replicon / Q000187:drug effects; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D011355:Prodrugs; D011684:Purine Nucleosides; D012367:RNA, Viral