Synthesis and structure-activity relationships of novel anti-hepatitis C agents: N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one derivatives.
Several 6- and 7-monosubstituted N3,5'-cyclo-4-(beta-d-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one derivatives as well as the 5-thiono analogue were synthesized, providing structure-anti-hepatitis C virus (HCV) activity relationships for the series. Among the compounds synthesized, the 6-bromo, 7-methylamino, and 5-thiono analogues exhibited more potent anti-HCV activity in an HCV subgenomic replicon cell based assay (EC90 = 1.9, 7.4, and 10.0 microM, respectively) than the lead compound N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one (EC90 = 79.8 microM).
Wang
Peiyuan
P
Pharmasset Inc., Princeton, New Jersey 08540, USA. peiyuan.wang@pharmasset.com
Du
Jinfa
J
Rachakonda
Suguna
S
Chun
Byoung-Kwon
BK
Tharnish
Phillip M
PM
Stuyver
Lieven J
LJ
Otto
Michael J
MJ
Schinazi
Raymond F
RF
Watanabe
Kyoichi A
KA
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012367:RNA, Viral / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D001952:Bridged-Ring Compounds; D009705:Nucleosides; D012367:RNA, Viral