The discovery of asunaprevir (BMS-650032), an orally efficacious NS3 protease inhibitor for the treatment of hepatitis C virus infection

Journal of Medicinal Chemistry

Volumn 57, Issue 5, 2014, Pages 1730-1752

  Scola, Paul M ^a   Sun, Li Qiang ^a   Wang, Alan Xiangdong ^a   Chen, Jie ^a   Sin, Ny ^a   Venables, Brian L ^a   Sit, Sing Yuen ^a   Chen, Yan ^a   Cocuzza, Anthony ^a   Bilder, Donna M ^a   D'Andrea, Stanley V ^a   Zheng, Barbara ^a   Hewawasam, Piyasena ^a   Tu, Yong ^a   Friborg, Jacques ^a   Falk, Paul ^a   Hernandez, Dennis ^a   Levine, Steven ^a   Chen, Chaoqun ^a   Yu, Fei ^a   Sheaffer, Amy K ^a   Zhai, Guangzhi ^a   Barry, Diana ^a   Knipe, Jay O ^a   Han, Yong Hae ^a   Schartman, Richard ^a   Donoso, Maria ^a   Mosure, Kathy ^a   Sinz, Michael W ^a   Zvyaga, Tatyana ^a   Good, Andrew C ^a   Rajamani, Ramkumar ^a   Kish, Kevin ^a   Tredup, Jeffrey ^a   Klei, Herbert E ^a   Gao, Qi ^a   Mueller, Luciano ^a   Colonno, Richard J ^a   Grasela, Dennis M ^a   Adams, Stephen P ^a   Loy, James ^a   Levesque, Paul C ^a   Sun, Huabin ^a   Shi, Hong ^a   Sun, Lucy ^a   Warner, William ^a   Li, Danshi ^a   Zhu, Jialong ^a   Meanwell, Nicholas A ^a   McPhee, Fiona ^a   more..

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASUNAPREVIR; DACLATASVIR; PEGINTERFERON; RIBAVIRIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DOG; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG EFFICACY; DRUG HALF LIFE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; HUMAN CELL; ISOLATED HEART; MALE; MAXIMUM PLASMA CONCENTRATION; MOLECULE; NONHUMAN; PHARMACOLOGICAL PARAMETERS; PHASE 3 CLINICAL TRIAL; RABBIT; RAT;

ANIMALS; ANTIVIRAL AGENTS; DOGS; HEPATITIS C; HUMANS; ISOQUINOLINES; MODELS, MOLECULAR; PROTEASE INHIBITORS; RABBITS; RATS; SULFONAMIDES; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84896292745     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500297k     Document Type: Article

References (60)

1. Scola, P. M.; Wang, A.; Good, A. C; Sun, L.; Combrink, K. D.; Campbell, J. A.; Chen, J.; Tu, Y.; Sin, N.; Venables, B. L.; Sit, S. Y.; Chen, Y.; Cocuzza, A.; Bilder, D. M.; D'Andrea, S.; Zheng, B.; Hewawasam, P.; Ding, M.; Thuring, J.; Hernandez, D.; Yu, F.; Falk, P.; Zhai, G.; Sheaffer, A. K.; Chen, C.; Lee, M. S.; Barry, D.; Knipe, J. O.; Han, Y. H.; Jenkins, S.; Gesenberg, C.; Sinz, M. W.; Santone, K. S.; Zvyaga, T.; Rajamani, R.; Klei, H. E.; Colonno, R. J.; Grasela, D. M.; Hughes, E.; Chien, C.; Adams, S.; Levesque, P. C.; Li, D.; Zhu, J.; Meanwell, N. A.; McPhee, F. Discovery and early clinical evaluation of BMS-605339, a potent and orally efficacious tripeptidic acylsulfonamide NS3 protease inhibitor for the treatment of hepatitis C virus infection. J. Med. Chem. 2014, DOI 10.1021/jm401840s.
2. Johansson, A.; Poliakov, A.; Kerblom, E. A; Wiklund, K.; Lindeberg, G.; Winiwarter, S.; Danielson, U. H.; Samuelsson, B.; Hallberg, A. Acyl sulfonamides as potent protease inhibitors of the hepatitis C virus full-length NS3 (protease-helicase/NTPase): a comparative study of different C-terminals Bioorg. Med. Chem. 2003, 11, 2551-2568
3. Oertqvist, P.; Peterson, S. D.; Aakerblom, E.; Gossas, T.; Sabnis, Y. A.; Fransson, R.; Lindeberg, G.; Danielson, U. H.; Karlen, A.; Sandstroem, A. Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors Bioorg. Med. Chem. 2007, 15, 1448-1474
4. Roenn, R.; Gossas, T.; Sabnis, Y. A.; Daoud, H.; Aakerblom, E.; Danielson, U. H.; Sandstroem, A. Evaluation of a diverse set of potential P1 carboxylic acid bioisosteres in hepatitis C virus NS3 protease inhibitors Bioorg. Med. Chem. 2007, 15, 4057-4068
5. Baeck, M.; Johansson, P.-O.; Waangsell, F.; Thorstensson, F.; Kvarnstroem, I.; Ayesa, S.; Waehling, H.; Pelcman, M.; Jansson, K.; Lindstroem, S.; Wallberg, H.; Classon, B.; RydergaÌŠrd, C.; Vrang, L.; Hamelink, E.; Hallberg, A.; Rosenquist, A.; Samuelsson, B. Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease: use of cyclopentane and cyclopentene P2-motifs Bioorg. Med. Chem. 2007, 15, 7184-7202
6. Naud, J.; Lemke, C.; Goudreau, N.; Beaulieu, E.; White, P. D.; Llinas-Brunet, M.; Forgione, P. Potent triazolyl-proline-based inhibitors of HCV NS3 protease Bioorg. Med. Chem. Lett. 2008, 18, 3400-3404
7. Raboisson, P.; de Kock, H.; Rosenquist, A.; Nilsson, M.; Salvador-Oden, L.; Lin, T.-I.; Roue, N.; Ivanov, V.; Wahling, H.; Wickstrom, K.; Hamelink, E.; Edlund, M.; Vrang, L.; Vendeville, S.; Van de Vreken, W.; 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
8. Cummings, M. D.; Lindberg, J.; 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
9. Raboisson, P.; Lin, T.-I.; de Kock, H.; Vendeville, S.; Van de Vreken, W.; McGowan, D.; Tahri, A.; Hu, L.; Lenz, O.; Delouvroy, F.; Surleraux, D.; Wigerinck, P.; Nilsson, M.; Rosenquist, A.; Samuelsson, B.; Simmen, K. Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine protease inhibitors Bioorg. Med. Chem. Lett. 2008, 18, 5095-5100
10. Vendeville, S.; Nilsson, M.; de Kock, H.; Lin, T.-I.; Antonov, D.; Classon, B.; Ayesa, S.; Ivanov, V.; Johansson, P.-O.; Kahnberg, P.; Eneroth, A.; Wikstrom, K.; Vrang, L.; Edlund, M.; Lindström, S.; Van de Vreken, W.; McGowan, D.; Tahri, A.; Hu, L.; Lenz, O.; Delouvroy, F.; Van Dooren, M.; Kindermans, N.; Surleraux, D.; Wigerinck, P.; Rosenquist, A.; Samuelsson, B.; Simmen, K.; Raboisson, P. Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors Bioorg. Med. Chem. Lett. 2008, 18, 6189-6193
11. Nilsson, M.; Belfrage, A. K.; Lindstroem, S.; Waehling, H.; Lindquist, C.; Ayesa, S.; Kahnberg, P.; Pelcman, M.; Benkestock, K.; Agback, T.; Vrang, L.; Terelius, Y.; Wikström, K.; Hamelink, E.; RydergaÌŠrd, C.; Edlund, M.; Eneroth, A.; Raboisson, P.; Lin, T.-I.; de Kock, H.; Wigerinck, P.; Simmen, K.; Samuelsson, B.; Rosenquist, A. Synthesis and SAR of potent inhibitors of the hepatitis C virus NS3/4A protease: exploration of P2 quinazoline substituents Bioorg. Med. Chem. Lett. 2010, 20, 4004-4011
12. Lampa, A.; Ehrenberg, A. E.; Gustafsson, S. S.; Vema, A.; Aakerblom, E.; Lindeberg, G.; Karlen, A.; Danielson, U. H.; Sandstroem, A. Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents Bioorg. Med. Chem. 2010, 18, 5413-5424
13. Oertqvist, P.; Gising, J.; Ehrenberg, A. E.; Vema, A.; Borg, A.; Karlen, A.; Larhed, M.; Danielson, U. H; Sandstroem, A. Discovery of achiral inhibitors of the hepatitis C virus NS3 protease based on 2(1 H)-pyrazinones Bioorg. Med. Chem. 2010, 18, 6512-6525
14. Oertqvist, P.; Vema, A.; Ehrenberg, A. E.; Dahl, G.; Roenn, R.; Aekerblom, E.; Karlen, A.; Danielson, U. H.; Sandstroem, A. Structure-activity relationships of HCV NS3 protease inhibitors evaluated on the drug-resistant variants A156T and D168V Antiviral Ther. 2010, 15, 841-852
15. Ding, C. Z.; Zhang, Y.-K.; Li, X.; Liu, Y.; Zhang, S.; Zhou, Y.; Plattner, J. J.; Baker, S. J.; Liu, L.; Duan, M.; Jarvest, R. L.; Ji, J.; Kazmierski, W. M.; Tallant, M. D.; Wright, L. L.; Smith, G. K.; Crosby, R. M.; Wang, A. A.; Ni, Z.-J.; Zoue, W.; Wright, J. Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease Bioorg. Med. Chem. Lett. 2010, 20, 7317-7322
16. Duan, M.; Kazmierski, W.; Crosby, R.; Gartland, M.; Ji, J.; Tallant, M.; Wang, A.; Hamatake, R.; Wright, L.; Wu, M.; Zhang, Y.-K.; Ding, C. Z.; Li, X.; Liu, Y.; Zhang, S.; Zhou, Y.; Plattner, J. J.; Baker, S. J. Discovery of novel P3-oxo inhibitor of hepatitis C virus NS3/4A serine protease Bioorg. Med. Chem. Lett. 2012, 22, 2993-2996
17. Kazmierski, W. M.; Hamatake, R.; Duan, M.; Wright, L. L.; Smith, G. K.; Jarvest, R. L.; Ji, J.-J.; Cooper, J. P.; Tallant, M. D.; Crosby, R. M.; Creech, K.; Wang, A.; Li, X.; Zhang, S.; Zhang, Y.-Y.; Liu, Y.; Ding, C. Z.; Zhou, Y.; Plattner, J. J.; Baker, S. J.; Bu, W.; Liu, L. Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor- resistant mutants J. Med. Chem. 2012, 55, 3021-3026
18. McCauley, J. A.; McIntyre, C. J.; Rudd, M. T.; Nguyen, K. T.; Romano, J. J.; Butcher, J. W.; Gilbert, K. F.; Bush, K. J.; Holloway, M. K.; Swestock, J.; Wan, B.-L.; Carroll, S. S.; DiMuzio, J. M.; Graham, D. J.; Ludmerer, S. W.; Mao, S.-S.; Stahlhut, M. W.; Fandozzi, C. M.; Trainor, N.; Olsen, D. B.; Vacca, J. P.; Liverton, N. J. Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor J. Med. Chem. 2010, 53, 2443-2463
19. Liverton, N. J.; Holloway, M. K.; McCauley, J. A.; Rudd, M. T.; Butcher, J. W.; Carroll, S. S.; DiMuzio, J.; Fandozzi, C.; Gilbert, K. F.; Mao, S.-S.; McIntyre, C. J.; Nguyen, K. T.; Romano, J. J.; Stahlhut, M.; Wan, B.-L.; Olsen, D. B.; Vacca, J. P. Molecular modeling based approach to potent P2-P4 macrocyclic inhibitors of hepatitis C NS3/4A protease J. Am. Chem. Soc. 2008, 130, 4607-4609
20. McCauley, J. A.; Rudd, M. T.; Nguyen, K. T.; McIntyre, C. J.; Romano, J. J.; Bush, K. J.; Varga, S. L.; Ross, C. W.; Carroll, I. I. I.; DiMuzio, S. S.; Stahlhut, J.; Olsen, M. W.; Lyle, D. B.; Vacca, T. A.; Liverton, J. P.; Bismacrocyclic, N. J. Inhibitors of hepatitis C NS3/4a protease Angew. Chem., Int. Ed. 2008, 47, 9104-9107
21. Harper, S.; Ferrara, M.; Crescenzi, B.; Pompei, M.; Palumbi, M. C.; Di Muzio, J. M.; Donghi, M.; Fiore, F.; Koch, U.; Liverton, N. J.; Pesci, S.; Petrocchi, A.; Rowley, M.; Summa, V.; Gardelli, C. Inhibitors of the hepatitis C virus NS3 protease with basic amine functionality at the P3-amino acid N-terminus: discovery and optimization of a new series of P2-P4 macrocycles J. Med. Chem. 2009, 52, 4820-4837
22. Di Francesco, M. E.; Dessole, G.; Nizi, E.; Pace, P.; Koch, U.; Fiore, F.; Pesci, S.; Di Muzio, J.; Monteagudo, E.; Rowley, M.; Summa, V. Novel macrocyclic inhibitors of hepatitis C NS3/4A protease featuring a 2-amino-1,3-thiazole as a P4 carbamate replacement J. Med. Chem. 2009, 52, 7014-7028
23. Rudd, M. T.; McCauley, J. A.; Butcher, J. W.; Romano, J. J.; McIntyre, C. J.; Nguyen, K. T.; Gilbert, K. F.; Bush, K. J.; Holloway, M. K.; Swestock, J.; Wan, B.-L.; Carroll, S. S.; DiMuzio, J. M.; Graham, D. J.; Ludmerer, S. W.; Stahlhut, M. W.; Fandozzi, C. M.; Trainor, N.; Olsen, D. B.; Vacca, J. P.; Liverton, N. J. Discovery of MK-1220: a macrocyclic inhibitor of hepatitis C virus NS3/4A protease with improved preclinical plasma exposure ACS Med. Chem. Lett 2011, 2, 207-212
24. 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, 332-336
25. Rudd, M. T.; McCauley, J. A.; Romano, J. J.; Butcher, J. W.; Bush, K.; McIntyre, C. J.; Nguyen, K. T.; Gilbert, K. F.; Lyle, T. A.; Holloway, M. K; Wan, B.-L.; Vacca, J. P.; Summa, V.; Harper, S.; Rowley, M.; Carroll, S. S.; Burlein, C.; DiMuzio, J. M.; Gates, A.; Graham, D. J.; Huang, Q.; Ludmerer, S. W.; McClain, S.; McHale, C.; Stahlhut, M.; Fandozzi, C.; Taylor, A.; Trainor, N.; Olsen, D. B.; Liverton, N. J. Development of potent macrocyclic inhibitors of genotype 3a HCV NS3/4A protease Bioorg. Med. Chem. Lett. 2012, 22, 7201-7206
26. Rudd, M. T.; McIntyre, C. J.; Romano, J. J.; Butcher, J. W.; Holloway, M. K.; Bush, K.; Nguyen, K. T.; Gilbert, K. F.; Lyle, T. A.; Liverton, N. J.; Wan, B.-L; Summa, V.; Harper, S.; Rowley, M.; Vacca, J. P.; Carroll, S. S.; Burlein, C.; DiMuzio, J. M.; Gates, A.; Graham, D. J.; Huang, Q.; Ludmerer, S. W.; McClain, S.; McHale, C.; Stahlhut, M.; Fandozzi, C.; Taylor, A.; Trainor, N.; Olsen, D. B.; McCauley, J. A. Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2-P4 linkers Bioorg. Med. Chem. Lett. 2012, 22, 7207-7213
27. Li, X.; Liu, Y.; Zhang, Y.-K.; Plattner, J. J.; Baker, S. J.; Bu, W.; Liu, L.; Zhou, Y.; Ding, C. Z.; Zhang, S.; Kazmierski, W. M.; Hamatake, R.; Duan, M.; Wright, L. L.; Smith, G. K.; Jarvest, R. L.; Ji, J.-J.; Cooper, J. P.; Tallant, M. D.; Crosby, R. M.; Creech, K.; Wang, A. Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4 capping groups Bioorg. Med. Chem. Lett. 2012, 22, 7351-7356
28. Bilodeau, F.; Bailey, M. D.; Bhardwaj, P. K.; Bordeleau, J.; Forgione, P.; Garneau, M.; Ghiro, E.; Gorys, V.; Halmos, T.; Jolicoeur, E. S.; Leblanc, M.; Lemke, C. T.; Naud, J.; O'Meara, J.; White, P. W.; Llinàs-Brunet, M. Synthesis and optimization of a novel series of HCV NS3 protease inhibitors: 4-arylproline analogs Bioorg. Med. Chem. Lett. 2013, 23, 4267-4271
29. Bailey, M. D.; Halmos, T.; Lemke, C. T. Discovery of novel P2 substituted 4-biaryl proline inhibitors of hepatitis C virus NS3 serine protease Bioorg. Med. Chem. Lett. 2013, 23, 4436-4440
30. Bailey, M. D.; Bordeleau, J.; Garneau, M.; Leblanc, M.; Lemke, C. T.; O'Meara, J.; White, P. W.; Llinas-Brunet, M. Peptide backbone replacement of hepatitis C virus NS3 serine protease C-terminal cleavage product analogs: Discovery of potent succinamide inhibitors Bioorg. Med. Chem. Lett. 2013, 23, 4447-4452
31. Moreau, B.; O'Meara, J. A.; Bordeleau, J.; Garneau, M.; Godbout, C.; Gorys, V.; Leblanc, M.; Villemure, E.; White, P. W.; Llinas-Brunet, M. Discovery of hepatitis C Virus NS3-4A protease inhibitors with improved barrier to resistance and favorable liver distribution. J. Med. Chem. 2014, DOI: 10.1021/jm400121t.
32. 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, 4432-4441
33. Jiang, Y.; Andrews, S. W.; Condroski, K. R.; Buckman, B.; Serebryany, V.; Wenglowsky, S.; Kennedy, A. L.; Madduru, M. R.; Wang, B.; Lyon, M.; Doherty, G. A.; Woodard, B. T.; Lemieux, C.; Geck Do, M.; Zhang, H.; Ballard, J.; Vigers, G.; Brandhuber, B. J.; Stengel, P.; Josey, J. A.; Beigelman, L.; Blatt, L.; Seiwert, S. D. Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease J. Med. Chem. 2014, 10.1021/jm400164c
34. McPhee, F.; Sheaffer, A. K.; Friborg, J.; Hernandez, D.; Falk, P.; Zhai, G.; Levine, S.; Chaniewski, S.; Yu, F.; Barry, D.; Chen, C.; Lee, M. S.; Mosure, K.; Sun, L.-Q.; Sinz, M.; Meanwell, N. A.; Colonno, R. J.; Knipe, J.; Scola, P. Preclinical profile and characterization of the hepatitis C virus NS3 protease inhibitor asunaprevir (BMS-650032) Antimicrob. Agents Chemother. 2012, 56, 5387-5396
35. Langendorff, O. Untersuchungen am uberleberden saugerleizen Puflger's Arch. Ges. Physiol. 1895, 61, 291-332
36. Pietschmann, T.; Bartenschlager, R. The hepatitis C virus replicon system and its application to molecular studies Curr. Opin. Drug Discovery Dev. 2001, 4, 657-664
37. Murray, M. Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation Curr. Drug Metab. 2000, 1, 67-84
38. Peterson, L. A. Reactive metabolites in the biotransformation of molecules containing a furan ring Chem. Res. Toxicol. 2013, 26, 6-25
39. Riley, R. J.; Grime, K.; Weaver, R. Time-dependent CYP inhibition Expert Opin. Drug Metab. Toxicol. 2007, 3, 51-566
40. Lindenbach, B. D.; Rice, C. M. Unravelling hepatitis C virus replication from genome to function Nature 2005, 436, 933-938
41. Reddy, M. B.; Morcos, P. N.; Le Pogam, S.; Ou, Y.; Frank, K.; Lave, T.; Smith, P. Pharmacokinetic/pharmacodynamic predictors of clinical potency for hepatitis C virus nonnucleoside polymerase and protease inhibitors Antimicrob. Agents Chemother. 2012, 56, 3144-3156
42. Reviriego, C. Asunaprevir: HCV serine protease NS3 inhibitor treatment of hepatitis C virus Drugs Future 2012, 37, 247-254
43. McPhee, F.; Friborg, J.; Levine, S.; Chen, C.; Falk, P.; Yu, F.; Hernandez, D.; Lee, M. S.; Chaniewski, S.; Sheaffer, A. K.; Pasquinelli, C. Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir Antimicrob. Agents Chemother. 2012, 56, 3670-3681
44. Balimane, P.; Browning, M.; Chong, S.; Dai, R.; Darienzo, R.; Dalterio, C.; Davis, C.; Han, Y.-H.; Kim, S.; Knipe, J.; Malinowski, J.; Marino, T.; Mosure, K.; Sandquist, J.; Gesenberg, C.; Schartman, R.; Sinz, M.; Whiterock, V.; Zadjura, L.; Zoeckler, M.; Zvyaga, T.; Meanwell, N. A.; McPhee, F.; Scola, P. M. Nonclinical pharmacokinetics of a novel HCV NS3 protease inhibitor, BMS-605339. Manuscript in preparation.
45. Pasquinelli, C.; McPhee, F.; Eley, T.; Villegas, C.; Sandy, K.; Sheridan, P.; Persson, A.; Huang, S.-P.; Hernandez, D.; Sheaffer, A. K.; Scola, P.; Marbury, T.; Lawitz, E.; Goldwater, R.; Rodriguez-Torres, M.; DeMicco, M.; Wright, D.; Charlton, M.; Kraft, W. K.; Lopez-Talavera, J.-C.; Grasela, D. M. Single- and multiple-ascending-dose studies of the NS3 protease inhibitor asunaprevir in subjects with or without chronic hepatitis C Antimicrob. Agents Chemother. 2012, 56, 1838-1844
46. Bronowicki, J.-P.; Pol, S.; Thuluvath, P. J.; Larrey, D.; Martorell Claudia, T.; Rustgi Vinod, K.; Morris, D. W.; Younes, Z.; Fried, M. W.; Bourliere, M.; Hezode, C.; Reddy, K. R.; Massoud, O.; Abrams, G. A.; Ratziu, V.; He, B.; Eley, T.; Ahmad, A.; Cohen, D.; Hindes, R.; McPhee, F.; Reilly, B.; Mendez, P.; Hughes, E. Randomized study of asunaprevir plus peg-interferon alfa and ribavirin for previously untreated genotype 1 chronic hepatitis C. Antivir. Ther. 2013, 18, 885-893.
47. Lok, A. S.; Gardiner, D. F.; Lawitz, E.; Martorell, C.; Everson, G. T.; Ghalib, R.; Reindollar, R.; Rustgi, V.; McPhee, F.; Wind-Rotolo, M.; Persson, A.; Zhu, K.; Dimitrova, D. I.; Eley, T.; Guo, T.; Grasela, D. M.; Pasquinelli, C. Preliminary study of two antiviral agents for hepatitis C genotype 1 N. Engl. J. Med. 2012, 366, 216-224
48. Lok, A. S.; Gardiner, D. F.; Hézode, C.; Lawitz, E. J.; Bourlière, M.; Everson, G. T.; Marcellin, P.; Rodriguez-Torres, M.; Pol, S.; Serfaty, L.; Eley, T.; Huang, S.-P.; Li, J.; Wind-Rotolo, M.; Yu, F.; McPhee, F.; Grasela, D. M.; Pasquinelli, C. Randomized trial of daclatasvir and asunaprevir with or without peginterferon/ribaviran for hepatitis C virus genotype 1 null responders J. Hepatol. 2014, 60, 490-499
49. Chayama, K.; Takahashi, S.; Toyota, J.; Karino, Y.; Ikeda, K.; Ishikawa, H.; Watanabe, H.; McPhee, F.; Hughes, E.; Kumada, H. Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders Hepatology 2012, 55, 742-748
50. Everson, G. T.; Sims, K. D.; Rodriguez-Torres, M.; Hézode, C.; Lawitz, E.; Bourlière, M.; Loustaud-Ratti, V.; Rustgi, V.; Schwartz, H.; Tatum, H.; Marcellin, P.; Pol, S.; Thuluvath, P. J.; Eley, T.; Wang, X.; Huang, S.-P.; McPhee, F.; Wind-Rotolo, M.; Chung, E.; Pasquinelli, C.; Grasela, D. M.; Gardiner, D. F. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naÏve patients with HCV genotype 1 infection. Gastroenterology 2013, 146, 420-429
51. Chung, R. T. A watershed moment in the treatment of hepatitis C N. Engl. J. Med. 2012, 366, 273-275
52. Suzuki, Y.; Ikeda, K.; Suzuki, F.; Toyota, J.; Karino, Y.; Chayama, K.; Kawakami, Y.; Ishikawa, H.; Watanabe, H.; Hu, W.; Eley, T.; McPhee, F.; Hughes, E.; Kumada, H. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options J. Hepatol. 2013, 58, 655-662
53. Gao, M.; Nettles, R. E.; Belema, M.; Snyder, L. B.; Nguyen, V. N.; Fridell, R. A.; Serrano-Wu, M. H.; Langley, D. R.; Sun, J.-H.; O'Boyle, D. R., II; Lemm, J. A.; Wang, C.; Knipe, J. O.; Chien, C.; Colonno, R. J.; Grasela, D. M.; Meanwell, N. A.; Hamann, L. G. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect Nature 2010, 465, 96-100
54. Campbell, J. A.; Good, A. World Patent Application WO-2002/060926 A2, 8 Aug 2002.
55. Crystal structure data has been deposited to Cambridge Structure Database (deposition number CCDC 984267).
56. Crespi, C. L.; Miller, V. P.; Penman, B. W. Microtiter plate assay for inhibition of human, drug-metabolizing cytochromes P450 Anal. Biochem. 1997, 248, 188-190
57. Klei, H. E.; Kish, K.; Russo, M. F.; Michalczyk, S. J.; Cahn, M. H.; Tredup, J.; Chang, C. Y.; Khan, J.; Baldwin, E. T. Image annotation and database mining to create a novel screen for the chemotype-dependent crystallization of HCV NS3 protease Cryst. Growth Des. 2011, 11, 1143-1151
58. Otwinowski, Z.; Minor, W. Processing of X-Ray Diffraction Data Collected in Oscillation Mode Methods Enzymol. 1997, 263, 307-326
59. QUANTA Modeling Environment; Accelrys, Inc: San Diego, CA, 2000.
60. Brünger, A.; Adams, P.; Clore, G.; DeLano, W.; Gros, P.; Grosse-Kunstleve, R.; Jiang, J.-S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; Read, R. J.; Rice, L. M.; Simonson, T.; Warren, G. L. Crystallography and NMR System: A New Software Suite for Macromolecular Structure Determination Acta Crystallogr., Sect D: Biol. Crystallogr. 1998, D54, 905-921