title: Synthesis of stable isotope labeled analogs of the anti-hepatitis C virus nucleotide prodrugs PSI-7977 and PSI-352938.
abstract: In order to support bioanalytical LC/MS method development and plasma sample analysis in preclinical and clinical studies of the anti-hepatitis C-virus nucleotides, PSI-7977 and PSI-352938, the corresponding stable isotope labeled forms were prepared. These labeled compounds were prepared by addition reaction of the freshly prepared Grignard reagent (13)CD(3)MgI to the corresponding 2 '-ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2 '-C-(trideuterated-(13)C-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones.
authors: Pharmasset, Inc., 303A College Road East, Princeton, NJ 08540, USA. kwon.chun@pharmasset.com
authors: Byoung-Kwon
authors: BK
authors: Chun
authors: Jinfa
authors: J
authors: Du
authors: Hai-Ren
authors: HR
authors: Zhang
authors: Wonsuk
authors: W
authors: Chang
authors: Bruce S
authors: BS
authors: Ross
authors: Ying
authors: Y
authors: Jiang
authors: Donghui
authors: D
authors: Bao
authors: Christine L
authors: CL
authors: Espiritu
authors: Meg
authors: M
authors: Keilman
authors: Holly M Micolochick
authors: HM
authors: Steuer
authors: Phillip A
authors: PA
authors: Furman
authors: Michael J
authors: MJ
authors: Sofia
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003498:Cyclic P-Oxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054879:Halogenation; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D003498:Cyclic P-Oxides; D009705:Nucleosides; C556498:PSI 352938; D011355:Prodrugs; D014542:Uridine Monophosphate; D000069474:Sofosbuvir