- Synthesis of stable isotope labeled analogs of the anti-hepatitis C virus nucleotide prodrugs PSI-7977 and PSI-352938
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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 13CD3MgI to the corresponding 2′-ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2′-C-(trideuterated- 13C-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones. Copyright Pharmasset, Inc..
- Chun, Byoung-Kwon,Du, Jinfa,Zhang, Hai-Ren,Chang, Wonsuk,Ross, Bruce S.,Jiang, Ying,Bao, Donghui,Espiritu, Christine L.,Keilman, Meg,Steuer, Holly M. Micolochick,Furman, Phillip A.,Sofia, Michael J.
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p. 886 - 896
(2013/01/15)
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- N- [ (2 ' R) -2 ' -DEOXY-2 ' -FLUORO-2 ' -METHYL-P-PHENYL-5 ' -URIDYLYL] -L-ALANINE 1-METHYLETHYL ESTER AND PROCESS FOR ITS PRODUCTION
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Disclosed herein are nucleoside phosphoramidates of formula 4 and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. Disclosed is also a process for preparing compound represented by formula 4: (Formula 4) wherein P* represents a chiral phosphorus atom, which comprises: a) reacting an isopropyl-alanate, (Formula A), a di-X'-phenylphosphate, (Formula B), 2'-deoxy-2f-fluoro-2'-C-methyluridine, (Formula 3), and a base to obtain a first mixture comprising 4; wherein X is a conjugate base of an acid, n is 0 or 1, and X' is a halogen, b) reacting the first mixture with a protecting compound to obtain a second mixture comprising 4; and c) optionally subjecting the second mixture to crystallization, chromatography or extraction in order to obtain 4.
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Page/Page column 68-69
(2010/12/18)
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