Discovery of a luoro-2′-β- C -methyluridine Nucleotide Prodrug (PSI-7977) for the treatment of hepatitis C virus

Journal of Medicinal Chemistry

Volumn 53, Issue 19, 2010, Pages 7202-7218

  Sofia, Michael J ^a   Bao, Donghui ^a   Chang, Wonsuk ^a   Du, Jinfa ^a   Nagarathnam, Dhanapalan ^a   Rachakonda, Suguna ^a   Reddy, P Ganapati ^a   Ross, Bruce S ^a   Wang, Peiyuan ^a   Zhang, Hai Ren ^a   Bansal, Shalini ^a   Espiritu, Christine ^a   Keilman, Meg ^a   Lam, Angela M ^a   Steuer, Holly M Micolochick ^a   Niu, Congrong ^a   Otto, Michael J ^a   Furman, Phillip A ^a  

^a PHARMASSET INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [(2,4 DICHLOROPHENOXY) [5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; 2 [(3,4 DICHLOROPHENOXY) [5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; 2 [(4 BROMOPHENOXY) [5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; 2 [4 (CHLOROPHENOXY) [5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY](NAPHTHALEN 1 YLOXY)PHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]ETHOXYPHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO] 3 METHYLBUTYRIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO] 3 PHENYLPROPIONIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO] 4 METHYLPENTANOIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO] 4 METHYLSULFANYLBUTYRIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO]BUTYRIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID ETHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID ISOPROPYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY](4 FLUOROPHENOXY)PHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID 2,2 DIFLUOROETHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID 4 FLUOROBENZYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID BENZYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID ISOPROPYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID PHENYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID PROPIONIC ACID 2 FLUOROETHYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID PROPIONIC ACID BUTYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID PROPIONIC ACID CYCLOHEXYL ESTER; 2 [[5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL)FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YL YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID PROPIONIC ACID PENTYL ESTER; 2' DEOXY 2' FLUORO 2' C METHYLURIDINE; [5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY]PHENOXYPHOSPHORYLAMINO]PROPIONIC ACID METHYL ESTER; PHOSPHORAMIDIC ACID DERIVATIVE; PSI 7976; PSI 7977; UNCLASSIFIED DRUG; UNINDEXED DRUG; URIDINE DERIVATIVE; 2 ((5 (2,4 DIOXO 3,4 DIHYDRO 2H PYRIMIDIN 1 YL) 4 FLUORO 3 HYDROXY 4 METHYLTETRAHYDROFURAN 2 YLMETHOXY)PHENOXYPHOSPHORYLAMINO)PROPIONIC ACID ISOPROPYL ESTER; 2' DEOXY 2' FLUORO 2' C METHYLURIDINE 5' MONOPHOSPHATE; 2'-DEOXY-2'-FLUORO-2'-C-METHYLURIDINE 5'-MONOPHOSPHATE; 2-((5-(2,4-DIOXO-3,4-DIHYDRO-2H-PYRIMIDIN-1-YL)-4-FLUORO-3-HYDROXY-4-METHYLTETRAHYDROFURAN-2-YLMETHOXY)PHENOXYPHOSPHORYLAMINO)PROPIONIC ACID ISOPROPYL ESTER; ANTIVIRUS AGENT; DRUG DERIVATIVE; ESTER; NS 5 PROTEIN, HEPATITIS C VIRUS; NS-5 PROTEIN, HEPATITIS C VIRUS; PRODRUG; URIDINE PHOSPHATE; VIRUS PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIASTEREOISOMER; DOG; DRUG POTENCY; ENZYME ACTIVITY; FIRST PASS EFFECT; HEPATITIS C; HEPATITIS C VIRUS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIVER CELL; MAXIMUM PLASMA CONCENTRATION; MONKEY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; POLYMERASE CHAIN REACTION; RAT; REPLICON; RNA REPLICATION; STEREOCHEMISTRY; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRUS GENOME; VIRUS REPLICATION; X RAY ANALYSIS; ANIMAL; ANTIVIRAL RESISTANCE; CELL LINE; DRUG ANTAGONISM; DRUG EFFECT; GENETICS; HUMAN; IN VITRO STUDY; LIVER; MACACA; METABOLISM; MUTATION; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ANIMALS; ANTIVIRAL AGENTS; CELL LINE; CRYSTALLOGRAPHY, X-RAY; DOGS; DRUG RESISTANCE, VIRAL; ESTERS; HEPACIVIRUS; HEPATOCYTES; HUMANS; LIVER; MACACA FASCICULARIS; MUTATION; PRODRUGS; RATS; REPLICON; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; URIDINE MONOPHOSPHATE; VIRAL NONSTRUCTURAL PROTEINS;

EID: 77957913871     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100863x     Document Type: Article

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