Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein

Bioorganic and Medicinal Chemistry Letters

Volumn 24, Issue 10, 2014, Pages 2288-2294

  Tai, Vincent W F ^a   Garrido, Dulce ^a   Price, Daniel J ^a   Maynard, Andrew ^a   Pouliot, Jeffrey J ^a   Xiong, Zhiping ^a   Seal, John W ^a   Creech, Katrina L ^a   Kryn, Luz H ^a   Baughman, Todd M ^a   Peat, Andrew J ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Hepatitis C virus (HCV); NS4B; Pyrazolo 1,5 a pyridine; Replication inhibitors; Spirocyclic ketals

Indexed keywords

ACETAL DERIVATIVE; ANTIVIRUS AGENT; HYDROXYL GROUP; NONSTRUCTURAL PROTEIN 4B; OXAZOLIDINONE DERIVATIVE; PIPERIDINE DERIVATIVE; NS4B PROTEIN, FLAVIVIRUS; SPIRO COMPOUND; VIRUS PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; DRUG CLEARANCE; DRUG DESIGN; DRUG HALF LIFE; DRUG PENETRATION; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SOLUBILITY; DRUG SYNTHESIS; DRUG TARGETING; GENE MUTATION; GENOTYPE; HEPATITIS C VIRUS; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PROTEIN TARGETING; RAT; REPLICON; VIRUS INHIBITION; VIRUS REPLICATION; CHEMISTRY; DRUG EFFECTS; HEPACIVIRUS; METABOLISM; MOLECULARLY TARGETED THERAPY; PHYSIOLOGY; SYNTHESIS;

HEPATITIS C VIRUS;

ANTIVIRAL AGENTS; DRUG DESIGN; HEPACIVIRUS; HUMANS; MOLECULAR TARGETED THERAPY; SPIRO COMPOUNDS; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84899628504     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2014.03.080     Document Type: Article

References (34)

1. G.L. Davis, J.E. Albright, S.F. Cook, and D.M. Rosenberg Liver Transplant. Off Publ. Am. Assoc. Study Liver Dis. Int. Liver Transplant. Soc. 9 2003 331
2. G.L. Armstrong, A. Wasley, E.P. Simard, G.M. McQuillan, W.L. Kuhnert, and M.J. Alter Ann. Intern. Med. 144 2006 705
3. World Health Organization fact sheet 164, July 2013, http://www.who.int/ mediacentre/factsheets/fs164/en/index.html.
4. A.D. Kwong, R.S. Kauffman, P. Hurter, and P. Mueller Nat. Biotechnol. 29 2011 993
5. S. Venkatraman Trends Pharmacol. Sci. 33 2012 289
6. K.X. Chen, and F.G. Njoroge Prog. Med. Chem. 49 2010 1
7. R. Bartenschlager, M. Frese, and T. Pietschmann Adv. Virus Res. 63 2004 71
8. S. Chevaliez, and J.-M. Pawlotsky Horizon Biosci. 2006 5
9. M.J. Sofia, W. Chang, P.A. Furman, R.T. Mosley, and B.S. Ross J. Med. Chem. 55 2012 2481
10. P.L. Yang, M. Gao, K. Lin, Q. Liu, and V.A. Villareal Curr. Opin. Virol. 1 2011 607
11. E.H. Sklan, and J.S. Glenn Hepatitis C Viruses 2006 Horizon Bioscience p. 245
12. R. Rai, and J. Deval Antiviral Res. 90 2011 93
13. J. Gouttenoire, F. Penin, and D. Moradpour Rev. Med. Virol. 20 2010 117
14. S. Li, X. Yu, Y. Guo, and L. Kong Cell. Microbiol. 14 2012 994
15. Z. Gu, J.D. Graci, F.C. Lahser, J.J. Breslin, S.P. Jung, J.H. Crona, P. McMonagle, E. Xia, S. Liu, G. Karp, J. Zhu, S. Huang, A. Nomeir, M. Weetall, N.G. Almstead, S.W. Peltz, X. Tong, R. Ralston, and J.M. Colacino Antimicrob. Agents Chemother. 57 2013 3250
16. X. Zhang, N. Zhang, G. Chen, A. Turpoff, H. Ren, J. Takasugi, C. Morrill, J. Zhu, C. Li, W. Lennox, S. Paget, Y. Liu, N. Almstead, N. George, Z. Gu, T. Komatsu, V. Clausen, C. Espiritu, J. Graci, J. Colacino, F. Lahser, N. Risher, M. Weetall, A. Nomeir, and G.M. Karp Bioorg. Med. Chem. Lett. 23 2013 3947
17. Banka, A.; Baskaran, S.; Catalano, J.; Chong, P.; Dickson, H.; Fang, J.; Maung, J.; Neitzel, M. L.; Peat, A.; Price, D.; Rai, R.; Roberts, C. D.; Shotwell, B.; Tai, V.; Zhang, H. WO 2010091411A1.
18. J.F. Miller, P.Y. Chong, J.B. Shotwell, J.G. Catalano, V.W.-F. Tai, J. Fang, A.L. Banka, C.D. Roberts, M. Youngman, H. Zhang, Z. Xiong, A. Mathis, J.J. Pouliot, R.K. Hamatake, D.J. Price, J.W. Seal, L.L. Stroup, K.L. Creech, L.H. Carballo, D. Todd, A. Spaltenstein, S. Furst, Z. Hong, and A.J. Peat J. Med. Chem. 57 2014 2107
19. J.B. Shotwell, S. Baskaran, P. Chong, K.L. Creech, R.M. Crosby, H. Dickson, J. Fang, D. Garrido, A. Mathis, J. Maung, D.J. Parks, J.J. Pouliot, D.J. Price, R. Rai, J.W. Seal, U. Schmitz, V.W.F. Tai, M. Thomson, M. Xie, Z.Z. Xiong, and A.J. Peat ACS Med Chem. Lett. 3 2012 565
20. B. Phillips, R. Cai, W. Delaney, Z. Du, M. Ji, H. Jin, J. Lee, J. Li, A. Niedziela-Majka, M. Mish, H.-J. Pyun, J. Saugier, N. Tirunagari, J. Wang, H. Yang, Q. Wu, C. Sheng, and C. Zonte J. Med. Chem. 57 2014 2161
21. R. Kakarla, J. Liu, D. Naduthambi, W. Chang, R.T. Mosley, D. Bao, H.M.M. Steuer, M. Keilman, S. Bansal, A.M. Lam, W. Seibel, S. Neilson, P.A. Furman, and M.J. Sofia J. Med. Chem. 57 2014 2136
22. Einav, S.; Glenn, J. S.; McDowell, R.; Yang, W. WO 2009039248A2.
23. X-ray crystallographic data of compounds 1 and 18 can be found at Cambridge Structural Database (CSD), the deposition numbers are CCDC 970777 and CCDC 970778, respectively.
24. F. Perron, and K.F. Albizati Chem. Rev. 89 1989 1617
25. H. Wissmann, and H.J. Kleiner Angew. Chem. 92 1980 129
26. F.X. Tavares, D.N. Deaton, L.R. Miller, and L.L. Wright J. Med. Chem. 47 2004 5057
27. M.C. Murguia, S.E. Vaillard, and R.J. Grau Synthesis 2001 1093
28. R.N. Loy, and E.N. Jacobsen J. Am. Chem. Soc. 131 2009 2786
29. C.S. Beshara, A. Hall, R.L. Jenkins, K.L. Jones, T.C. Jones, N.M. Killeen, P.H. Taylor, S.P. Thomas, and N.C.O. Tomkinson Org. Lett. 7 2005 5729
30. E. Palovics, F. Faigl, and E. Fogassy InTech 2012 3
31. The corresponding six membered 1,3-oxazinan-2-one analogs are less active.
32. A.P. Hill, and D.J. Young Drug Discovery Today 15 2010 648
33. P. Ertl, B. Rohde, and P. Selzer J. Med. Chem. 43 2000 3714
34. P.D. Leeson, and B. Springthorpe Nat. Rev. Drug Disc. 6 2007 881