title: Design and evaluation of a potential mutagen for Hepatitis C virus.
abstract: Pyrrolopyrimidine nucleoside 1 was designed and synthesized as a potential mutagen for HCV. An in vitro HCV NS5B enzymatic assay indicated that pyrrolopyrimidine triphosphate acts as a CTP analog rather than a UTP analog. The SATE-prodrug of pyrrolopyrimidine monophosphate showed a weak inhibitory activity in an HCV replicon system (EC(50)=60 microM) and did not exhibit cytotoxicity (CC(50)>100 microM). Investigation of phosphorylation events using nucleoside kinases and LC-MS analysis revealed that the second phosphorylation step, from monophosphate ester to diphosphate ester, is unfavorable.
authors: Valeant Pharmaceutical Research & Development, 3300 Hyland Ave., Costa Mesa, CA 92626, USA. ykoh@andreabiosciences.com
authors: Yung-Hyo
authors: YH
authors: Koh
authors: Jae Hoon
authors: JH
authors: Shim
authors: Jean-Luc
authors: JL
authors: Girardet
authors: Zhi
authors: Z
authors: Hong
mesh_terms: D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D009153:Mutagens / Q000494:pharmacology*; D010766:Phosphorylation; D014779:Virus Replication / Q000187:drug effects
chemical_list: D009153:Mutagens