ANIMAL EXPERIMENT;
ARTICLE;
CONTROLLED STUDY;
DOG;
DRUG BIOAVAILABILITY;
DRUG CLEARANCE;
DRUG IDENTIFICATION;
DRUG STRUCTURE;
DRUG SYNTHESIS;
HEPATITIS C VIRUS;
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY;
LIVER;
MASS SPECTROMETRY;
NONHUMAN;
PROTON NUCLEAR MAGNETIC RESONANCE;
RAT;
RING CLOSING METATHESIS;
SINGLE DRUG DOSE;
World Health Organization (WHO). Initiative for Vaccine Research. Hepatitis C. http://www.who.int/vaccine-research/diseases/viral-cancers/en/ index2.html
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection
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Treating viral hepatitis C: Efficacy, side effects, and complications
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Peptidomimetic Therapeutic Agents Targeting the Protease Enzyme of the Human Immunodeficiency Virus and Hepatitis C Virus
Reviewed in: (a)
Reviewed in: (a) Tsantrizos, Y. S. Peptidomimetic Therapeutic Agents Targeting the Protease Enzyme of the Human Immunodeficiency Virus and Hepatitis C Virus. Acc. Chem. Res. 2008, 41 (10), 1252-1263.
Advances in the development of new therapeutic agents targeting the NS3-4A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus
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Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease
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An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus
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Structure-Activity Study on a Novel Series of Macrocyclic Inhibitors of the Hepatitis C Virus NS3 Protease Leading to the Discovery of BILN 2061
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Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease
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Discovery and development of VX-950, a novel, covalent, and reversible inhibitor of hepatitis C virus NS3.4A serine protease
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Discovery of (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor: A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection
Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350
(a) Raboisson, P.; De Kock, H.; Rosenquist, Å.; Nilsson, M.; Salvador-Oden, L.; Lin, T.; Roue, N.; Ivanov, V.; Wähling, H.; Wickström, K.; Hamelink, E.; Edlung, M.; Vrang, L.; Vendeville, S.; Van de Vreken, W. V.; McGowan, D.; Tahri, A.; Hu, L.; Boutton, C.; Lenz, O.; Delouvroy, F.; Pille, G.; Surleraux, D.; Wigerinck, P.; Samuelsson, B.; Simmen, K. Structure-activity relationship study on a novel series of cyclopentane- containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg. Med. Chem. Lett. 2008, 18, 4853-4858.
Press releases at the Tibotec homepage: accessed Jul 2009
New Data on Tibotec Investigational Hepatitic C Compounds being Presented at EASL. Press releases at the Tibotec homepage: http://www.tibotec.com/news/ detail.jhtml?action=view&itemname=news-60 (accessed Jul 2009).
Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227)
(a) Seiwert, S. D.; Andrews, S. W.; Jiang, Y.; Serebryany, V.; Tan, H.; Kossen, K.; Rajagopalan, P. T. R.; Misialek, S.; Stevens, S. K.; Stoycheva, A.; Hong, J.; Lim, S. R.; Qin, X.; Rieger, R.; Condroski, K. R.; Zhang, H.; Do, M. G.; Lemieux, C.; Hingorani, G. P.; Hartley, D. P.; Josey, J. A.; Pan, L.; Beigelman, L.; Blatt, L. M. Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227). Antimicrob. Agents Chemother. 2008, 52 (12), 4432-4441.
Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of HCV replication
PCT Int. Appl. WO 2005/037214
(b) Blatt, L. M.; Wenglowsky, S. M.; Andrews, S. W.; Jiang, Y.; Kennedy, A. L.; Condroski, K. R.; Josey, J. A.; Stengel, P. J.; Madduru, M. R.; Doherty, G. A.; Woodard, B. T. Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of HCV replication. PCT Int. Appl. WO 2005/037214, 2005.
Synthesis of Two Novel Cyclic Biphenyl Ether Analogs of an Inhibitor of HCV NS3 Protease
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Design, Synthesis, and Biological Activity of m-Tyrosine-Based 16- And 17-Membered Macrocyclic Inhibitors of Hepatitis C Virus NS3 Serine Protease
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Molecular modeling based approach to potent P2-P4 macrocyclic inhibitors of hepatitis C NS3/4a protease
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Bismacrocyclic inhibitors of hepatitis C NS3/4a protease
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Preparation of peptides as hepatitis C virus inhibitors
PCT Int. Appl. WO 2005/051410
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Discovery of MK-7009:a novel macrocyclic HCV NS3/4A protease inhibitor
Abstracts of Papers
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Preparation of peptidyl macrocyclic compounds as antiviral agents
PCT Int. Appl. WO 2007/131966
Di Francesco, M. E.; Nizi, E.; Pace, P.; Summa, V. Preparation of peptidyl macrocyclic compounds as antiviral agents. PCT Int. Appl. WO 2007/131966, 2007.
The Zhan ruthenium metathesis catalyst RC-301, Zhan catalyst 1, dichloro(5-chloro-2-isopropoxybenzylidene)(1,3-dimethylimidazolidin-2-ylidene) ruthenium, is available from Strem, catalogue no. 44-0082. (Chemical Equation Presented)
The Zhan ruthenium metathesis catalyst RC-301, Zhan catalyst 1, dichloro(5-chloro-2-isopropoxybenzylidene)(1,3-dimethylimidazolidin-2-ylidene) ruthenium), is available from Strem, catalogue no. 44-0082. (Chemical Equation Presented)
47
71049144474
Hepatitis C Virus Inhibitors
U.S. Patent 6,995,174
Wang, X. A.; Sun, L.-Q.; Sit, S.-Y.; Sin, N.; Scola, P. M.; Hewawasam, P.; Good, A. C.; Chen, Y.; Campbell, J. A. Hepatitis C Virus Inhibitors. U.S. Patent 6,995,174, 2006.
Preparation of macrocyclic compounds as HCV NS3 protease inhibitors
PCT Int. Appl. WO 2006/119061
Holloway, M. K.; Liverton, N. J.; Ludmerer, S. W.; McCauley, J. A.; Olsen, D. B.; Rudd, M. T.; Vacca, J. P. Preparation of macrocyclic compounds as HCV NS3 protease inhibitors. PCT Int. Appl. WO 2006/119061, 2006.
Preparation of macrocyclic compounds as HCV NS3 protease inhibitors
US 2007/027071
Holloway, M. K.; Liverton, N. J.; Ludmerer, S. W.; Mccauley, J. A.; Olsen, D. B.; Rudd, M. T.; Vacca, J. P.; Mcintyre, C. J. Preparation of macrocyclic compounds as HCV NS3 protease inhibitors. US 2007/027071, 2007.
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A time-resolved, internally quenched fluorescence assay to characterize inhibition of hepatitis C virus nonstructural protein 3-4A protease at low enzyme concentrations
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More than 10 analogues featuring the oxadiazole moiety in P4 were prepared bearing combinations of the various P2 cores and P3 residues. Overall they proved to be inferior to the corresponding aminothiazoles, in analogy with the findings described for analogue 4
More than 10 analogues featuring the oxadiazole moiety in P4 were prepared bearing combinations of the various P2 cores and P3 residues. Overall they proved to be inferior to the corresponding aminothiazoles, in analogy with the findings described for analogue 4.
54
0032560602
Potent Peptide Inhibitors of Human Hepatitis C Virus NS3 Protease Are Obtained by Optimizing the Cleavage Products
(a) Ingallinella, P.; Altamura, S.; Bianchi, E.; Taliani, M.; Ingenito, R.; Cortese, R.; De Francesco, R.; Steinkuehler, C.; Pessi, A. Potent Peptide Inhibitors of Human Hepatitis C Virus NS3 Protease Are Obtained by Optimizing the Cleavage Products. Biochemistry 1998, 37 (25), 8906-8914.
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Peptide-based inhibitors of the hepatitis C virus serine protease
(b) Llinas-Brunet, M.; Bailey, M.; Fazal, G.; Goulet, S.; Halmos, T.; Laplante, S.; Maurice, R.; Poirier, M.; Poupart, M.; Thibeault, D.;Wernic, D.; Lamarre, D. Peptide-based inhibitors of the hepatitis C virus serine protease. Bioorg. Med. Chem. Lett. 1998, 8 (13), 1713-1718.
A Systematic Approach to the Optimization of Substrate-Based Inhibitors of the Hepatitis C Virus NS3 Protease: Discovery of Potent and Specific Tripeptide Inhibitors
Llinas-Brunet, M.; Bailey, M. D.; Ghiro, E.; Gorys, V.; Halmos, T.; Poirier, M.; Rancourt, J.; Goudreau, N. A Systematic Approach to the Optimization of Substrate-Based Inhibitors of the Hepatitis C Virus NS3 Protease: Discovery of Potent and Specific Tripeptide Inhibitors. J. Med. Chem. 2004, 47 (26), 6584-6594.
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Solid-Phase Synthesis of Peptidomimetic Inhibitors for the Hepatitis C Virus NS3 Protease
(b) Poupart, M.; Cameron, D. R.; Chabot, C.; Ghiro, E.; Goudreau, N.; Goulet, S.; Poirier, M.; Tsantrizos, Y. S. Solid-Phase Synthesis of Peptidomimetic Inhibitors for the Hepatitis C Virus NS3 Protease. J. Org. Chem. 2001, 66 (14), 4743-4751.
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Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3-4A protease inhibitors in treatmentnaive subjects
Bartels, D. J.; Zhou, Y.; Zhang, E. Z.; Marcial, M.; Byrn, R. A.; Pfeiffer, T.; Tigges, A. M.; Adiwijaya, B. S.; Lin, C.; Kwong, A. D.; Kieffer, T. L. Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3-4A protease inhibitors in treatmentnaive subjects. J. Infect. Dis. 2008, 198 (6), 800-807.
