Structure-Activity Relationships in the Development of Allosteric Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibitors: Ten Years of Research

Synthesis and SAR studies of novel heteroaryl fused tetracyclic indole-diamide compounds: Potent allosteric inhibitors of the hepatitis C virus NS5B polymerase

(2012) Min Ding et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A Novel Class of Highly Potent Irreversible Hepatitis C Virus NS5B Polymerase Inhibitors

(2012) Kevin X. Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles

(2011) Gopinadhan N. Anilkumar et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The Synthesis and evaluation of a novel class of (E)-3-(1-cyclohexyl-1H-pyrazol-3-yl)-2-methylacrylic acid Hepatitis C virus polymerase NS5B inhibitors

(2011) Scott W. Martin et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The discovery and structure–activity relationships of pyrano[3,4-b]indole-based inhibitors of hepatitis C virus NS5B polymerase

(2011) Randy W. Jackson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Hepatitis C NS5B polymerase inhibitors: Functional equivalents for the benzothiadiazine moiety

(2011) Douglas K. Hutchinson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

SAR studies on a series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides: Potent inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus

(2011) Robert G. Gentles et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

From benzimidazole to indole-5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase. Part 1: Indole C-2 SAR and discovery of diamide derivatives with nanomolar potency in cell-based subgenomic replicons

(2011) Pierre L. Beaulieu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Indole 5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase with nanomolar potency in cell-based subgenomic replicons (part 2): Central amino acid linker and right-hand-side SAR studies

(2011) Pierre L. Beaulieu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase

(2011) Robert G. Gentles et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus

(2011) Xiaofan Zheng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

II. Novel HCV NS5B polymerase inhibitors: Discovery of indole C2 acyl sulfonamides

(2011) Gopinadhan N. Anilkumar et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

3-Heterocyclyl quinolone inhibitors of the HCV NS5B polymerase

(2011) Dange V. Kumar et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of Naturally Occurring Aurones That Are Potent Allosteric Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase

(2011) Romain Haudecoeur et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure–Activity Relationship (SAR) Development and Discovery of Potent Indole-Based Inhibitors of the Hepatitis C Virus (HCV) NS5B Polymerase

(2011) Kevin X. Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

The synthesis of novel heteroaryl-fused 7,8,9,10-tetrahydro-6H-azepino[1,2-a]indoles, 4-oxo-2,3-dihydro-1H-[1,4]diazepino[1,7-a]indoles and 1,2,4,5-tetrahydro-[1,4]oxazepino[4,5-a]indoles. Effective inhibitors of HCV NS5B polymerase

(2011) Min Ding et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Structure-based virtual screening, synthesis and SAR of novel inhibitors of hepatitis C virus NS5B polymerase

(2010) Tanaji T. Talele et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Allosteric inhibitors of hepatitis C virus NS5B polymerase thumb domain site II: Structure-based design and synthesis of new templates

(2010) Savina Malancona et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Benzimidazole Thumb Pocket I finger-loop inhibitors of HCV NS5B polymerase: Improved drug-like properties through C-2 SAR in three sub-series

(2010) Pierre L. Beaulieu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Inhibitors of hepatitis C virus polymerase: Synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides

(2010) Cliff C. Cheng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

N-Acetamideindolecarboxylic acid allosteric ‘finger-loop’ inhibitors of the hepatitis C virus NS5B polymerase: discovery and initial optimization studies

(2010) Pierre L. Beaulieu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Cyclic amide bioisosterism: Strategic application to the design and synthesis of HCV NS5B polymerase inhibitors

(2010) Hanbiao Yang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Quinolones as HCV NS5B polymerase inhibitors

(2010) Dange V. Kumar et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of (7R)-14-Cyclohexyl-7-{[2-(dimethylamino)ethyl](methyl) amino}-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic Acid (MK-3281), a Potent and Orally Bioavailable Finger-Loop Inhibitor of the Hepatitis C Virus NS5B Polymerase

(2010) Frank Narjes et al.   JOURNAL OF MEDICINAL CHEMISTRY

Importance of Ligand Bioactive Conformation in the Discovery of Potent Indole-Diamide Inhibitors of the Hepatitis C Virus NS5B

(2010) Steven R. LaPlante et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Pyridine Carboxamides: Potent Palm Site Inhibitors of HCV NS5B Polymerase

(2010) Cliff C. Cheng et al.   ACS Medicinal Chemistry Letters

HCV NS5B polymerase inhibitors 2: Synthesis and in vitro activity of (1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl) azolo[1,5-a]pyridine and azolo[1,5-a]pyrimidine derivatives

(2009) Guangyi Wang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase

(2009) Frank Ruebsam et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Pyrazolo[1,5-a]pyrimidine-based inhibitors of HCV polymerase

(2009) Janeta Popovici-Muller et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

1,5-Benzodiazepine inhibitors of HCV NS5B polymerase

(2009) David McGowan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of 4H-pyrazolo[1,5-a]pyrimidin-7-ones as potent inhibitors of hepatitis C virus polymerase

(2009) Yongqi Deng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: Synthesis and optimization studies of benzothiazine-substituted tetramic acids

(2009) Javier de Vicente et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Non-nucleoside inhibitors of HCV polymerase NS5B. Part 4: Structure-based design, synthesis, and biological evaluation of benzo[d]isothiazole-1,1-dioxides

(2009) Javier de Vicente et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Non-nucleoside inhibitors of HCV NS5B polymerase. Part 1: Synthetic and computational exploration of the binding modes of benzothiadiazine and 1,4-benzothiazine HCV NS5b polymerase inhibitors

(2009) Robert T. Hendricks et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Synthesis and biological activity of heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone derivatives as hepatitis C virus NS5B polymerase inhibitors

(2009) Rosanna Tedesco et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

HCV NS5B polymerase inhibitors 1: Synthesis and in vitro activity of 2-(1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene derivatives

(2009) Guangyi Wang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

5,5′- and 6,6′-Dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase

(2009) David A. Ellis et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure–activity relationships of benzothiazine-substituted quinolinediones

(2009) Javier de Vicente et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Substituted benzothiadizine inhibitors of Hepatitis C virus polymerase

(2009) Antony N. Shaw et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of benzimidazole-diamide finger loop (Thumb Pocket I) allosteric inhibitors of HCV NS5B polymerase: Implementing parallel synthesis for rapid linker optimization

(2009) Sylvie Goulet et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Optimization of Thienopyrrole-Based Finger-Loop Inhibitors of the Hepatitis C Virus NS5B Polymerase

(2009) Jose Ignacio Martin Hernando et al.   ChemMedChem

Slow Binding Inhibition and Mechanism of Resistance of Non-nucleoside Polymerase Inhibitors of Hepatitis C Virus

(2009) Julie Qi Hang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Inhibitors of Hepatitis C Virus Polymerase: Synthesis and Biological Characterization of Unsymmetrical Dialkyl-Hydroxynaphthalenoyl-benzothiadiazines

(2009) Rolf Wagner et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification and Biological Evaluation of a Series of 1H-Benzo[de]isoquinoline-1,3(2H)-diones as Hepatitis C Virus NS5B Polymerase Inhibitors‡

(2009) Jesus M. Ontoria et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis and Biological Characterization of B-Ring Amino Analogues of Potent Benzothiadiazine Hepatitis C Virus Polymerase Inhibitors

(2009) John T. Randolph et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Design of a Benzodiazepine Scaffold Yields a Potent Allosteric Inhibitor of Hepatitis C NS5B RNA Polymerase

(2009) Koen Vandyck et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of (R)-6-Cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor

(2009) Hui Li et al.   JOURNAL OF MEDICINAL CHEMISTRY

1,5-Benzodiazepines, a Novel Class of Hepatitis C Virus Polymerase Nonnucleoside Inhibitors

(2008) O. Nyanguile et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Molecular Mechanism of Hepatitis C Virus Replicon Variants with Reduced Susceptibility to a Benzofuran Inhibitor, HCV-796

(2008) A. Y. M. Howe et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Structure-based design, synthesis, and biological evaluation of 1,1-dioxoisothiazole and benzo[b]thiophene-1,1-dioxide derivatives as novel inhibitors of hepatitis C virus NS5B polymerase

(2008) Sun Hee Kim et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors

(2008) Stephen S. Antonysamy et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 3: Further optimization of the 2-, 6-, and 7′-substituents and initial pharmacokinetic assessments

(2008) Lian-Sheng Li et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Pyrrolo[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase

(2008) Frank Ruebsam et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones: Part 4. Optimization of DMPK properties

(2008) Maria V. Sergeeva et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

4-(1,1-Dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-ones as potent inhibitors of HCV NS5B polymerase

(2008) David A. Ellis et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Des-A-ring benzothiadiazines: Inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase

(2008) Pamela L. Donner et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase

(2008) Frank Ruebsam et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 5: Exploration of pyridazinones containing 6-amino-substituents

(2008) Peter S. Dragovich et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 2: Variation of the 2- and 6-pyridazinone substituents

(2008) Yuefen Zhou et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Hepatitis C NS5B polymerase inhibitors: 4,4-Dialkyl-1-hydroxy-3-oxo-3,4-dihydronaphthalene-3-yl benzothiadiazine derivatives

(2008) Douglas K. Hutchinson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 1: Exploration of 7′-substitution of benzothiadiazine

(2008) Yuefen Zhou et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

3-Hydroxyisoquinolines as inhibitors of HCV NS5b RNA-dependent RNA polymerase

(2008) Robert T. Hendricks et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

5,6-Dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase

(2008) Frank Ruebsam et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of pentacyclic compounds as potent inhibitors of hepatitis C virus NS5B RNA polymerase

(2008) Jörg Habermann et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Tetracyclic indole inhibitors of hepatitis C virus NS5B-polymerase

(2008) Ian Stansfield et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The Discovery of Pyrano[3,4-b]indole-Based Allosteric Inhibitors of HCV NS5B Polymerase with In Vivo Activity

(2008) Matthew G. LaPorte et al.   ChemMedChem

Non-Nucleoside Inhibitors of NS5B Polymerase Binding to Allosteric Sites: 3DQSAR and Molecular Docking Studies

(2008) Hongyu Cao et al.   CURRENT MEDICINAL CHEMISTRY

HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity In Vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus

(2008) Norman M. Kneteman et al.   HEPATOLOGY

Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV polymerase inhibitors

(2007) Todd D. Bosse et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS