Novel quinoline-based P2-P4 macrocyclic derivatives as pan-genotypic HCV NS3/4a protease inhibitors

ACS Medicinal Chemistry Letters

Volumn 5, Issue 3, 2014, Pages 264-269

  Shah, Unmesh ^a   Jayne, Charles ^a   Chackalamannil, Samuel ^a   Velázquez, Francisco ^a   Guo, Zhuyan ^a   Buevich, Alexei ^a   Howe, John A ^a   Chase, Robert ^a   Soriano, Aileen ^a   Agrawal, Sony ^a   Rudd, Michael T ^a   McCauley, John A ^a   Liverton, Nigel J ^a   Romano, Joseph ^a   Bush, Kimberly ^a   Coleman, Paul J ^a   Grisé Bard, Christiane ^a   Brochu, Marie Christine ^a   Charron, Sylvie ^a   Aulakh, Virender ^a   Bachand, Benoit ^a   Beaulieu, Patrick ^a   Zaghdane, Helmi ^a   Bhat, Sathesh ^a   Han, Yongxin ^a   Vacca, Joseph P ^a   Davies, Ian W ^a   Weber, Ann E ^a   Venkatraman, Srikanth ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Antiviral; genotype 3a; HCV; macrocycle; NS3 4a; pan genotypic

Indexed keywords

ANTIVIRUS AGENT; MACROCYCLIC COMPOUND; PROTEINASE INHIBITOR; QUINOLINE DERIVATIVE;

ALKYLATION; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; FOLLOW UP; HEPATITIS C VIRUS; HYDROLYSIS; MITSUNOBU REACTION; MOLECULAR MODEL; NONHUMAN; PRIORITY JOURNAL; RAT;

EID: 84896361851     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml400466p     Document Type: Article

References (14)

1. Armstrong, G. L.; Wasley, A.; Simard, E. P.; McQuillan, G. M.; Kuhnert, W. L.; Alter, M. J. The Prevalence of Hepatitis C Virus Infection in the United States, 1999 Through 2002 Ann. Intern. Med. 2006, 144, 705-714
2. Lavanchy, D. The Global Burden of Hepatitis C Liver Int. 2009, 29 (Suppl 1) 74-81
3. Deuffic-Burban, S.; Poynard, T.; Sulkowski, M. S.; Wong, J. B. Estimating the Future Health Burden of Chronic Hepatitis C and Human Immunodeficiency Virus Infections in the United States J. Viral Hepatitis 2007, 14, 107-115
4. Ghany, M. G.; Strader, D. B.; Thomas, D. L.; Seeff, L. B. Diagnosis, Management, and Treatment of Hepatitis C: An Update Hepatology 2009, 49, 1335-1374
5. Poordad, F.; McCone, J., Jr.; Bacon, B. R.; Bruno, S.; Manns, M. P.; Sulkowski, M. S; Jacobson, I. M.; Reddy, K. R.; Goodman, Z. D.; Boparai, N.; DiNubile, M. J.; Sniukiene, V.; Brass, C. A.; Albrecht, J. K.; Bronowicki, J. P. SPRINT-2 Investigators. Boceprevir for Untreated Chronic HCV Genotype 1 Infection N. Engl. J. Med. 2011, 364, 1195-1206
6. Jacobson, I. M.; McHutchison, J. G.; Dusheiko, G.; Di Bisceglie, A. M.; Reddy, K. R.; Bzowej, N. H.; Marcellin, P.; Muir, A. J.; Ferenci, P.; Flisiak, R.; George, J.; Rizzetto, M.; Shouval, D.; Sola, R.; Terg, R. A.; Yoshida, E. M.; Adda, N.; Bengtsson, L.; Sankoh, A. J.; Kieffer, T. L.; George, S.; Kauffman, R. S.; Zeuzem, S. ADVANCE Study Team. Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection N. Engl. J. Med. 2011, 364, 2405-2416
7. Kiser, J. J.; Flexner, C. Direct-Acting Antiviral Agents for Hepatitis C Virus Infection Annu. Rev. Pharmacol. Toxicol. 2013, 53, 427-449
8. Summa, V.; Ludmerer, S. W.; McCauley, J. A.; Fandozzi, C.; Burlein, C.; Claudio, G.; Coleman, P. J.; Dimuzio, J. M.; Ferrara, M.; DiFilippo, M.; Gates, A. T.; Graham, D. J.; Harper, S.; Hazuda, D. J.; McHale, C.; Monteagudo, E.; Pucci, V.; Rowley, M.; Rudd, M. T.; Soriano, A.; Stahlhut, M. W.; Vacca, J. P.; Olsen, D. B.; Liverton, N. J.; Carroll, S. S. MK-5172, a Selective Inhibitor of Hepatitis C Virus NS3/4a Protease With Broad Activity Across Genotypes and Resistant Variants Antimicrob. Agents Chemother. 2012, 56 (8) 4161-4167
9. Harper, S.; McCauley, J. A.; Rudd, M. T.; Ferrara, M.; DiFilippo, M.; Crescenzi, B.; Koch, U.; Petrocchi, A.; Holloway, M. K.; Butcher, J. W.; Romano, J. J.; Bush, K. J.; Gilbert, K. F.; McIntyre, C. J.; Nguyen, K. T.; Nizi, E.; Carroll, S. S.; Ludmerer, S. W.; Burlein, C.; DiMuzio, J. M.; Graham, D. J.; McHale, C. M.; Stahlhut, M. W.; Olsen, D. B.; Monteagudo, E.; Cianetti, S.; Giuliano, C.; Pucci, V.; Trainor, N.; Fandozzi, C. M.; Rowley, M.; Coleman, P. J.; Vacca, J. P.; Summa, V.; Liverton, N. J. Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor ACS Med. Chem. Lett. 2012, 3 (4) 332-336
10. Cummings, M. D.; Lindberg, J. D.; Lin, T.-I.; de Kock, H.; Lenz, O.; Lilja, E.; Fellander, S.; Baraznenok, V.; Nystrom, S.; Nilsson, M.; Vrang, L.; Edlund, M.; Rosenquist, A.; Samuelsson, B.; Raboisson, P.; Simmen, K. Induced-Fit Binding of the Macrocyclic Noncovalent Inhibitor TMC435 to its HCV NS3/NS4A Protease Target Angew. Chem., Int. Ed. 2010, 49, 1652-1655
11. Yao, N.; Reichert, P.; Taremi, S. S.; Prosise, W. W.; Weber, P. C. Molecular Views of Viral Polyprotein Processing Revealed by the Crystal Structure of the Hepatitis C Virus Bifunctional Protease-helicase Struct. Folding Des. 1999, 7, 1353-1363
12. Rudd, M. T.; McCauley, J.; Liverton, N.; Grise-Bard, C.; Brouchu, M.-C.; Charron, S.; Aulakh, V.; Bachand, B.; Beaulieu, P.; Zaghdane, H.; Han, Y.; Ferrara, M.; Harper, S.; Summa, V.; Chackalamannil, S.; Venkatraman, S.; Shah, U.; Velazquez, F. Preparation of Macrocyclic Quinoline and Naphthyridine Peptides as HCV NS3 Protease Inhibitors Useful in the Treatment of Hepatitis C Infection. WO Pat. Appl. 2013074386, 2013.
13. The HCV NS3 protease inhibitory activity was measured using the protease time-resolved fluorescence (TRF) assay described in WO Pat. Appl. 2006102087. Also see Supporting Information section for detailed description of the assay.
14. Shah, U. G.; Boyle, C. D.; Chackalamannil, S.; Neustadt, B. R.; Harris, J. M.; Stamford, A.; Greenlee, W. J.; Neelamkavil, S. F. Preparation of Pyrimidinylazabicyclooctane Derivatives and Analogs for Use as GPCR Modulators. WO Pat. Appl. 2010075273, 2010.