A comprehensive insight into the chemical space and ADME features of small molecule NS5A inhibitors

Current Topics in Medicinal Chemistry

Volumn 16, Issue 12, 2016, Pages 1372-1382

  Ivanenkov, Yan A ^a,b,c,d   Veselov, Mark S ^a   Shakhbazyan, Artem G ^a   Aladinskiy, Vladimir A ^a   Aladinskaya, Anastasia V ^a   Yartseva, Sofya M ^a   Majouga, Alexander G ^d,e   Vantskul, Anton S ^a   Leonov, Sergey V ^a   Ivachtchenko, Alexandre V ^b   Koteliansky, Victor E ^d  

^a MOSCOW INSTITUTE OF PHYSICS AND TECHNOLOGY   (Russian Federation)

^b CHEMDIV INC   (United States)

^c Chemical Diversity Research Institute   (Russian Federation)

^d MOSCOW STATE UNIVERSITY   (Russian Federation)

^e NATIONAL UNIVERSITY OF SCIENCE AND TECHNOLOGY MISIS   (Russian Federation)

Author keywords

ADME; Antiviral; HCV; Inhibitors; NS5A; Pharmacokinetics

Indexed keywords

ASC 16; AV 4025; AZD 7295; CYTOCHROME P450; DACLATASVIR; ELBASVIR; GL 100953; GRAZOPREVIR; GSK 2336805; LEDIPASVIR; NONSTRUCTURAL PROTEIN 5A INHIBITOR; ODALASVIR; OMBITASVIR; PYRROLIDINE DERIVATIVE; SAMATASVIR; UNCLASSIFIED DRUG; VEDROPREVIR; VELPATASVIR; ANTIVIRUS AGENT; MOLECULAR LIBRARY; NS-5 PROTEIN, HEPATITIS C VIRUS; VIRAL PROTEIN;

ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG TRANSFORMATION; EC50; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LOCALIZATION; FLUORESCENCE RESONANCE ENERGY TRANSFER; HEPATITIS C; HEPATITIS C VIRUS; IC50; MAXIMUM PLASMA CONCENTRATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRUS REPLICATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; CONFORMATION; DRUG EFFECTS; HEPACIVIRUS; HUMAN; METABOLISM; MICROBIAL SENSITIVITY TEST; MOLECULAR LIBRARY; PHARMACOLOGY; SYNTHESIS;

ANIMALS; ANTIVIRAL AGENTS; HEPACIVIRUS; HUMANS; MICROBIAL SENSITIVITY TESTS; MOLECULAR CONFORMATION; SMALL MOLECULE LIBRARIES; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84961695969     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026616666151120113040     Document Type: Article

References (64)

1. WHO fact sheet N0 164. Hepatitis C. Updated July 2013. http://www.who.int/mediacentre/factsheets/fs164/en/, 2015.
2. Hepatitis C. Information for Health Professionals. http://www.cdc.gov/hepatitis/hcv/#, 2015.
3. Appel, N.; Schaller, T.; Penin, F.; Bartenschlager, R. From structure to function: new insights into hepatitis C virus RNA replication. J. Biol. Chem., 2006, 281, 9833−9836.
4. Macdonald, A.; Harris, M. Hepatitis C virus NS5A: tales of a promiscuous protein. J. Gen. Virol., 2004, 85, 2485−2502.
5. Szabo, G. Hepatitis C virus NS5A protein: a master regulator? Gastroenterology, 2006, 130, 996−999.
6. Ross-Thriepland, D.; Mankouri, J.; Harris, M. Serine phosphorylation of the hepatitis C virus NS5A protein controls the establishment of replication complexes. J. Virol. 2014. pii: JVI.02995-14. Available from: http://jvi.asm.org/content/early/2014/12/26/ JVI.02995-14.abstract, 2015.
7. Meistermann, H.; Gao, J.; Golling, S.; Lamerz, J.; Le Pogam S.; Tzouros, M.; Sankabathula, S.; Gruenbaum, L.; Najera, I.; Langen, H.; Klumpp, K.; Augustin, A. A novel immuno-competitive capture mass spectrometry strategy for protein-protein interaction profiling reveals that LATS kinases regulate HCV replication through NS5A phosphorylation. Mol. Cell Proteomics, 2014, 13(11), 3040−3048.
8. Ross-Thriepland, D.; Harris, M. Insights into the complexity and functionality of hepatitis C virus NS5A phosphorylation. J. Virol., 2014, 88(3), 1421−1432.
9. Cho, N.J.; Lee, C.; Pang, P.S.; Pham, E.A.; Fram, B.; Nguyen, K.; Xiong, A.; Sklan, E.H.; Elazar, M.; Koytak, E.S.; Kersten, C.; Kanazawa, K.K.; Frank, C.W.; Glenn, J.S. Phosphatidylinositol 4,5-bisphosphate is an HCV NS5A Ligand and Mediates Replication of the Viral Genome. Gastroenterology, 2015, 148(3), 616−625.
10. David, N.; Yaffe, Y.; Hagoel, L.; Elazar, M.; Glenn, J.S.; Hirschberg, K.; Sklan, E.H. The interaction between the Hepatitis C proteins NS4B and NS5A is involved in viral replication. Virology, 2015, 15(475), 139−149.
11. Lambert, S.M.; Langley, D.R.; Garnett, J.A.; Angell, R.; Hedgethorne, K.; Meanwell, N.A.; Matthews, S.J. The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors. Protein Sci., 2014 23(6):723−734.
12. Love, R.A.; Brodsky, O.; Hickey, M.J.; Wells, P.A.; Cronin, C.N. Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus. J. Virol., 2009, 83(9), 4395−4403.
13. Izumi, N. Efficacy of daclatasvir in hepatitis C virus. Expert Rev Anti Infect. Ther., 2014, 12(9), 1025−1031.
14. Adler, H.; Lambert, J.S. Daclatasvir for the treatment of hepatitis C virus infection. Expert Rev. Gastroenterol. Hepatol., 2014, 8(7), 725−738.
15. Thomson Integrity Database. http://integrity.thomson-pharma.com, 2015.
16. Serrano-Wu, M.; Belema, M.; Snyder, L.B.; Meanwell, N.; Denis St, L.; Kakaria, R.; Nguyen, V.N.; Qiu, Y.; Yang, X.; Leet, J.E.; Gao, M.; O'boyle, D.R.; Lemm, J.A.; Yang, F. Inhibitors of HCV replication. World Patent Application WO-2006/133326, December 14, 2006.
17. Gao, M.; Lemm, J.A.; O’Boyle, D.R.; Nower, P.; Rigat, K.; Sun, J.-H. Hepatitis C virus assays. World Patent Application WO-2004/015131, February 19, 2004.
18. Colonno, R.; Lemm, J.A.; O’Boyle, D.R.; Gao, M.; Romine, J.L.; Martin, S.W.; Snyder, L.B.; Serrano-Wu, M.; Deshpande, M.; Whitehouse, D. Combination pharmaceutical agents as inhibitors of HCV replication. World Patent Application WO-2004/014313, February 19, 2004.
19. Romine, J.L.; Martin, S.W.; Snyder, L.B.; Serrano-Wu, M.; Deshpande, M.; Whitehouse, D.; Lemm, J.; O’Boyle, D.R.; Gao, M.; Colonno, R. Iminothiazolidinones as inhibitors of HCV replication. World Patent Application WO-2004/014852, February 19, 2004.
20. Lemm, J.A.; O’Boyle, D.R., II; Liu, M.; Nower, P.T.; Colonno, R.; Deshpande, M.S.; Snyder, L.B.; Martin, S.W.; Laurent St, D.R.; Serrano-Wu, M.H.; Romine, J.L.; Meanwell, N.A.; Gao, M. Identification of hepatitis C virus NS5A inhibitors. J. Virol., 2010, 84, 482−491.
21. 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.
22. Lemm, J.A.; Leet, J.E.; O’Boyle, D.R., II; Romine, J.L.; Huang, X.S.; Schroeder, D.R.; Alberts, J.; Cantone, J.L.; Sun, J.-H.; Nower, P.T.; Martin, S.W.; Serrano-Wu, M.H.; Meanwell, N.A.; Snyder, L.B.; Gao, M. Discovery of potent hepatitis C virus NS5A inhibitors with dimeric structures. Antimicrob. Agents Chemother., 2011, 55, 3795−3802.
23. Romine, J.L.; Laurent St, D.R.; Leet, J.E.; Martin, S.W.; Serrano-Wu, M.H.; Yang, F.; Gao, M.; O’Boyle, D.R., II; Lemm, J.A.; Sun, J.-H.; Nower, P.T.; Huang, X.; Deshpande, M.S.; Meanwell, N.A.; Snyder, L.B. Inhibitors of HCV NS5A: from iminothiazolidinones to symmetrical stilbenes. ACS Med. Chem. Lett., 2011, 2, 224−229.
24. Giroux, S.; Xu, J.; Reddy, T.J.; Morris, M.; Cottrell, K.M.; Cadilhac, C.; Henderson, J.A.; Nicolas, O.; Bilimoria, D.; Denis, F.; Mani, N.; Ewing, N.; Shawgo, R.; L'Heureux, L.; Selliah, S.; Chan, L.; Chauret, N.; Berlioz-Seux, F.; Namchuk, M.N.; Grillot, A.L.; Bennani, Y.L.; Das, S.K.; Maxwell, J.P. Discovery of Thienoimidazole-Based HCV NS5A Genotype 1a and 1b Inhibitors. ACS Med. Chem. Lett., 2014, 5(3), 240–243.
25. Lopez, O.D.; Nguyen, V.N.; Laurent St, D.R.; Belema, M.; Serrano-Wu, M.H.; Goodrich, J.T.; Yang, F.; Qiu, Y.; Ripka, A.S.; Nower, P.T.; Valera, L.; Liu, M.; O’Boyle, D.R., II; Sun, J.-H.; Fridell, R.A.; Lemm, J.A.; Gao, M.; Good, A.C.; Meanwell, N.A.; Snyder, L.B. HCV NS5A replication complex inhibitors. Part 3: Discovery of potent analogs with distinct core topologies. Bioorg. Med. Chem. Lett., 2013, 23, 779−784.
26. Belema, M.; Nguyen, V. N.; Laurent St, D. R.; Lopez, O. D.; Qiu, Y.; Good, A. C.; Nower, P. T.; Valera, L.; O’Boyle, D. R., II; Sun, J.-H.; Fridell, R. A.; Lemm, J. A.; Gao, M.; Knipe, J. O.; Meanwell, N.A.; Snyder, L. B. HCV NS5A replication complex inhibitors. Part 5: Discovery of potent and pan-genotypic HCV NS5A replication complex inhibitors. Bioorg. Med. Chem. Lett., 2013, 23, 4428−4435.
27. Belema, M.; Nguyen, V.N.; Romine, J.L.; Laurent St, D.R.; Lopez, O.D.; Goodrich, J.; Nower, P.T.; O’Boyle, D.R., II; Lemm, J.A.; Fridell, R.A.; Gao, M.; Fang, H.; Krause, R.G.; Wang, Y.-K.; Oliver, A.J.; Good, A.C.; Knipe, J.O.; Meanwell, N.A.; Snyder, L.B. Hepatitis C virus NS5A replication complex inhibitors. Part 6: The discovery of a novel and highly potent biarylimidazole chemotype with inhibitory activity toward genotype 1a and 1b replicons. J. Med. Chem., 2014, 57(5), 1995−2012.
28. Ivachtchenko, A.V.; Mitkin, O.D.; Yamanushkin, P.M.; Kuznetsova, I.V.; Bulanova, E.A.; Shevkun, N.A.; Koryakova A.G.; Karapetian, R.N.; Bichko, V.V.; Trifelenkov, A.S.; Kravchenko, D.V.; Vostokova, N.V.; Veselov, M.S.; Chufarova, N.V.; Ivanenkov, Y.A. Discovery of novel highly potent hepatitis C virus NS5A inhibitor (AV4025). J. Med. Chem., 2014, 57(18), 7716−7730.
29. Belema, M.; Lopez, O.D.; Bender, J.A.; Romine, J.L.; Laurent, D.R. St.; Langley, D.R.; Lemm, J.A.; O’Boyle, D.R.; Sun, J.-H.; Wang, C.; Fridell, R.A.; Meanwell N.A. Discovery and Development of Hepatitis C Virus NS5A Replication Complex Inhibitors. J. Med. Chem., 2014, 57(5), 1643–1672.
30. Cordek, D.G.; Bechtel, J.T.; Maynard, A.T.; Kazmierski, W.M.; Cameron, C.E. Targeting the NS5A protein of HCV: an emerging option. Drugs Future, 2011, 36, 691−711.
31. Issur, M.; Götte, M. Resistance patterns associated with HCV NS5A inhibitors provide limited insight into drug binding. Viruses., 2014, 6(11), 4227−4241.
32. Nettles, J.H.; Stanton, R.A.; Broyde, J.; Amblard, F.; Zhang, H.; Zhou, L.; Shi, J.; McBrayer, T.R.; Whitaker, T.; Coats, S.J.; Kohler, J.J.; Schinazi, R.F. Asymmetric binding to NS5A by daclatasvir (BMS-790052) and analogs suggests two novel modes of HCV inhibition. J. Med. Chem., 2014, 57(23), 10031−10043.
33. Qiu, Y.-L.; Wang, C.; Cao, H.; Peng, H.; Ying, L.; Gao, X.; Or, Y.S. Hepatitis C virus inhibitors. World Patent Application WO-2013/052362, April 11, 2013.
34. Sofia, M.J.; Kakarla, R.; Liu, J.; Naduthambi, D.; Mosley, R.; Steuer, H.M. Pyrazine and imidazolidine derivatives and their uses to treat hepatitis C. U.S. Patent Application US-2012/202794, August 2, 2012.
35. Chai, D.; Duffy, K.J.; Fitch, D.M.; Shaw, A.N.; Tedesco, R.; Wiggall, K.J.; Zimmerman, M.N. Anti-infectives. World Patent Application, WO-2004/052312, June 24, 2004.
36. Moss, S.J.; Gregory, M.A.; Wilkinson, B.; Martin, C.J. Sanglifehrin based compounds. World Patent Application WO-2011/098809, August 18, 2011.
37. Moss S.J.; Bobardt M.; Leyssen P.; Coates N.; Chatterji U.; Dejian X.; Foster T.; Liu J.; Nur-e-Alam M.; Suthar D.; Yongsheng, C.; Warneck, T.; Zhang, M.-Q.; Neyts, J.; Gallay, P.; Wilkinson, B.; Gregory, M.A. Med. Chem. Commun., 2012, 3(8), 944−949.
38. Shang, L.; Lou, Z.; Wang, Y.; Zhao, Q.; Xu, M.; Yang, C.; Zhao, X.; Yin, Z.; Rao, Z. Anti-enterovirus 71 (EV71) valerolactam compounds, preparation method and uses thereof. Patent CN102838523, December 26, 2012.
39. Krueger, A.C.; Madigan, D.L.; Beno, D.W.; Betebenner, D.A.; Carrick, R.; Green, B.E.; He, W.; Liu, D.; Maring, C.J.; McDaniel, K.F.; Mo, H.; Molla, A.; Motter, C.E.; Pilot-Matias, T.J.; Tufano, M.D.; Kempf, D.J. Novel hepatitis C virus replicon inhibitors: synthesis and structure−activity relationships of fused pyrimidine derivatives. Bioorg. Med. Chem. Lett., 2012, 22(6), 2212−2215.
40. DeGoey, D.A.; Betebenner, D.A.; Grampovnik, D.J.; Iwasaki, N.; Liu, D.; Pratt, J.K.; Tufano, M.D.; He, W.; Krishnan, P.; Pilot-Matias, T.J.; Marsh, K.C; Molla, A.; Kempf, D.J.; Maring, C.J. In: Discovery of novel inhibitors of HCV NS5A and proof of concept study in an HCV-infected chimpanzee In: Proceedings of the 243rd ACS National Meeting, San Diego, USA, March 25−29, 2012, Abst. MEDI 169.
41. Angell, R.M.; Barners, M.C.; Cockerill, G.S.; Lumley, J.; Mathews, N.; Reynolds, K.; Tiberghien, N. Pyrazolopyrimidines as anti-hepatitis C agents. World Patent Application WO-2005/047288, May 26, 2005.
42. Bianco, A.; Reghellin, V.; Donnici, L.; Fenu, S.; Alvarez, R.; Baruffa, C.; Peri, F.; Pagani, M.; Abrignani, S.; Neddermann, P.; De Francesco, R. Metabolism of phosphatidylinositol 4-kinase IIIα-dependent PI4P is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity. PLoS Pathog., 2012, 8(3). Available from: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002576, 2015.
43. Wheelhouse, C.J.; Thomas, A. J.F.; Bushnell, D.J.; Lumley, J.; Salter, J.I.; Carter, M.C.; Mathews, N.; Pilkington, C.J.; Angell, R.M.: Biphenyl derivatives and their use in treating hepatitis C. World Patent Application WO-2007/031791, March 22, 2007.
44. Conte, I.; Giuliano, C.; Ercolani, C.; Narjes, F.; Koch, U.; Rowley, M.; Altamura, S.; De Francesco, R.; Neddermann, P.; Migliaccio, G.; Stansfield, I.: Synthesis and SAR of piperazinyl-Nphenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture. Bioorg. Med. Chem. Lett., 2009, 19(6), 1779−1783.
45. Conte, I.; Ercolani, C.; Guiliano, C.; Migliaccio, G.; Stansfield I. Modulators of HCV replication. World Patent Application WO-2006/038039, April 13, 2006.
46. Romine, J. L.; Martin, S. W.; Snyder, L. B.; Serrano-Wu, M.; Deshpande, M.; Whitehouse, D.; Lemm, J.; O’Boyle, D.; Gao, M.; Colonno, R. Iminothiazolidinones as inhibitors of HCV replication. World Patent Application WO-2004/014852, April 22, 2004.
47. Denghani M. A. A.; Griffith, R. C.; Leivers, M. R.; Rai, R.; Roberts, C. D.; Schmitz, F. U.; Slobodov, I. N-(5-membered heteroaromatic ring)-amido anti-viral compounds. World Patent Application WO-2007/070600, November 15, 2007.
48. Leivers M. R.; Schmitz F. U.; Griffith, R. C.; Roberts, C. D.; Denghani M. A. A.; Chan, S. A.; Rai, R.; Slobodov, I.; Ton, T. L. Amido anti-viral compounds. World Patent Application WO-2008/064218, May 29, 2008.
49. Cao, J.; Cho, H.-J..; Fathi, R.; Lam, A.; Li, G..; Liao, Y.; Nawoschik, K.; Ruoqiu, W.; Sandrasagra, A.; Wobbe, C. R.; Yang, Z.; Zhu, Q. Compounds and methods for treatment of HCV. World Patent Application WO-2008/048589, April 24, 2008.
50. Thomson Reuters Metadrug. http://thomsonreuters.com/metadrug/, 2015.
51. Amblard, F.; Zhang, H.; Zhou, L.; Shi, J.; Bobeck, D.R.; Nettles, J.H.; Chavre, S.; McBrayer, T.R.; Tharnish, P.; Whitaker, T.; Coats, S. J.; Schinazi, R.F.: Synthesis and evaluation of non-dimeric HCV NS5A inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(7), 2031−2034.
52. Mogalian, E.; Mathias, A.; Brainard, D.; Brainard, D.; McNally, J.; Moorehead L.; Hernandez, M.; Perry, R.; Curtis, C.; Lawitz, E.; Lasseter, K.; Marbury, T. In: The pharmacokinetics of GS-5816, a pan-genotypic HCV NSSA inhibitor, in HCV-uninfected subjects with moderate and severe hepatic impairment In: Proceedings of the 49th Annual Meeting of the European Association Study of the Liver (EASL), London, UK, April 9−13, 2014, Abst. P742.
53. Yeh, W.W.; Caro, L.; Guo, Z.; Feng, H.-P.; Davis, H.; Kozisek, M.; Stypinski, D.; Feng, C.; Mitchell, C.; Gillespie, A.; Ichhpurani, N.; Marshall, W.L.; Lasseter, K.C.; Marbury, T.C.; Butterton, J.R. In: Pharmacokinetics of co-administered HCV protease inhibitor MK-5172 and NS5A inhibitor MK-8742 in volunteers with endstage renal disease on hemodialysis or severe renal impairment not on hemodialysis In: Proceedings of the 65th Annual Meeting of the American Association for the Study of Liver Diseases, Boston, USA, November 7−11, 2014, Abst. 1940.
54. Wilfret, D.A.; Walker, J.; Adkison, K.K.; Jones, L.A.; Lou, Y.; Gan, J.; Castellino, S.; Moseley, C.L.; Horton, J.; de Serres, M.; Culp, A.; Goljer, I.; Spreen, W. Safety, tolerability, pharmacokinetics, and antiviral activity of GSK2336805, an inhibitor of hepatitis c virus (HCV) NS5A, in healthy subjects and subjects chronically infected with HCV genotype 1. Antimicrob. Agents Chemother., 2013, 57(10), 5037−5044.
55. Mogalian, E.; Mathias, A.; Yang, J.C.; Moorehead, L.; Hernandez, M.; Lasseter, K.; Ries, D.K.; Robson, R.A.; Klein, G.K.; In: The pharmacokinetics of ledipasvir, an HCV specific NS5A inhibitor, in HCV-uninfected subjects with severe renal impairment In: Proceedings of the 65th Annual Meeting of the American Association for the Study of Liver Diseases, Boston, USA, November 7−11, 2014, Abst. 1952.
56. Furihata, T.; Matsumoto, S.; Fu, Z.; Tsubota, A.; Sun, Y.; Matsumoto, S.; Kobayashi, K.; Chiba, K. Different interaction profiles of direct-acting anti-hepatitis C. Antimicrob. Agents Chemother., 2014, 58(8), 4555−4564.
57. German, P.; Mathias, A.; Yang, J.C.; McNair, L.; Shen, G.; Vimal, M.; Gane, E.J.; Smith, W.B.; Klein, G.K.; Marbury, T.C.; Lawitz, E. In: Pharmacokinetics of ledipasvir, an HCV specific NS5A inhibitor in HCV-uninfected subjects with moderate and severe hepatic impairment In: Proceedings of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, D.C., USA, November 1−5, 2013, Abst. 467.
58. Belema, M.; Meanwell, N.A. Discovery of daclatasvir, a pangenotypic hepatitis c virus NS5A replication complex inhibitor with potent clinical effect. J. Med. Chem., 2014, 57(12), 5057−5071.
59. Link, J.O.; Bannister, R.; Beilke, L.D.; Cheng, G.; Cornpropst, M.; Corsa, A.; Dowdy, E.; Guo, H.; Kato, D.; Kirschberg, T.; Liu, H.; Mitchell, M.; Matles, M.; Mogalian, E.; Mondou, E.; Ohmstede, C.; Peng, B.; Scott, R.; Findley, J.; Chittick, G.; Wang, F.; Alianti, J.; Sun, J.; Taylor, J.; Tian, Y., Xu, L.; Yang, C.; Yuen, G.; Wang, K.; Eisenburg, G. In: Nonclinical profile and phase I results in healthy volunteers for the novel and potent HCV NS5A inhibitor GS-5885 In: Proceedings of the 61st Annual Meeting of the American Association for the Study of Liver Diseases, Boston, USA, October 29 – November 2, 2010, Abst. 1883.
60. Coburn, C.A.; Meinke, P.T.; Chang, W.; Fandozzi, C.M.; Graham, D.J.; Hu, B.; Huang, Q.; Kargman, S.; Kozlowski, J.; Liu, R.; McCauley, J.A.; Nomeir, A.A.; Soll, R.M.; Vacca, J.P.; Wang, D.; Wu, H.; Zhong, B.; Olsen, D.B.; Ludmerer, S.W. Discovery of MK-8742: An HCV NS5A inhibitor with broad genotype activity. ChemMedChem, 2013, 8(12), 1930−1940.
61. DeGoey, D.A.; Betebenner, D.A.; Grampovnik, D.J.; Liu, D.; Pratt, J.K.; Tufano, M.D.; He, W.; Krishnan, P.; Pilot-Matias, T.J.; Marsh, K.C.; Molla, A.; Kempf, D.J.; Maring, C.J. Discovery of pyrido[2,3-d]pyrimidine-based inhibitors of HCV NS5A. Bioorg. Med. Chem. Lett., 2013, 23(12), 3627-3630.
62. DeGoey, D.A.; Randolph, J.T.; Liu, D.; Pratt, J.; Hutchins, C.; Donner, P.; Krueger, A.C.; Matulenko, M.; Patel, S.; Motter, C.E.; Nelson, L.; Keddy, R.; Tufano, M.; Caspi, D.D.; Krishnan, P.; Mistry, N.; Koev, G.; Reisch, T.J.; Mondal, R.; Pilot-Matias, T.; Gao, Y.; Beno, D.W.; Maring, C.J.; Molla, A.; Dumas, E.; Campbell, A.; Williams, L.; Collins, C.; Wagner, R.; Kati, W.M. Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J. Med. Chem., 2014, 57(5), 2047−2057.
63. Shi, J.X.; Zhou, L.H.; Amblard, F.; Bobeck, D.R.; Zhang, H.; Liu, P.; Bondada, L.; McBrayer, T.R.; Tharnish, P.M.; Whitaker, T.; Coats, S.J.; Schinazi, R.F. Synthesis and biological evaluation of new potent and selective HCV NS5A inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(10), 3488−3491.
64. Cheng, G.; Peng, B.; Corsa, A.; Yu, M.; Nash, M.; Lee, Y.J.; Xu, Y.; Kirschberg, T.; Tian, Y.; Taylor, J.; Link, J.; Delaney, W. In: Antiviral activity and resistance profile of the novel HCV NS5A inhibitor GS-5885 In: Proceedings of the 47th Annual Meeting of the European Association Study of the Liver (EASL), Barcelona, Spain, April 18−22, 2012, Abst. 1172.