Inhibitors of hepatitis C virus NS3/4A: α-Ketoamide based macrocyclic inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 8, 2009, Pages 2295-2298

  Avolio, Salvatore ^a   Robertson, Keith ^a   Hernando, Josè Ignacio Martin ^a   DiMuzio, Jillian ^b   Summa, Vincenzo ^a  

^a IRBM   (Italy)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Ketoamide; Hepatitis C; Macrocycle; NS3 serine protease; PK properties

Indexed keywords

ALPHA KETOAMIDE; BOCEPREVIR; CILUPREVIR; HEPATITIS C ANTIBODY; MACROCYCLIC COMPOUND; PROTEINASE INHIBITOR; SERINE; TELAPREVIR; UNCLASSIFIED DRUG;

ARTICLE; HEPATITIS C VIRUS; HEPATITIS C VIRUS 4A; HEPATITIS C VIRUS NS3; NONHUMAN; PROTEINASE INHIBITION; REACTION OPTIMIZATION; VIRUS INHIBITION; VIRUS REPLICATION;

AMIDES; ANIMALS; ANTIVIRAL AGENTS; CARRIER PROTEINS; HEPACIVIRUS; KETONES; MACROCYCLIC COMPOUNDS; MALE; PROTEASE INHIBITORS; RATS; RATS, WISTAR; SERINE PROTEINASE INHIBITORS; VIRAL NONSTRUCTURAL PROTEINS; VIRAL PROTEINS;

HEPATITIS C VIRUS;

EID: 63149089374     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.02.079     Document Type: Article

References (33)

1. World Health Organization (WHO). Fact Sheet No. 164, October 2000.
2. Liang T.J., and Heller T. Gastroenterology 127 (2004) S62
3. Feld J.J., and Hoofnagle J.H. Nature 436 (2005) 967
4. De Clerq E. Nat. Rev. Drug Disc. 6 (2007) 1001
5. De Francesco R., and Carfì A. Adv. Drug Delivery Rev. 59 (2007) 1242
6. Failla C., Tomei L., and De Francesco R. J. Virol. 68 (1994) 3753
7. Lin C., Kwong A.D., and Perni R.B. Infect. Disorder: Drug Targets 6 (2006) 3
8. Venkatraman S., Bogen S.L., Arasappan A., Bennet F., Chen K., Jao E., Liu Y.-T., Lovey R., Hendrata S., Huang Y., Pan W., Parekh T., Pinto P., Popov V., Pike R., Ruan S., Santhanam B., Vibulbhan B., Wu W., Yang W., Kong J., Liang X., Wong J., Liu R., Butkiewicz N., Chase R., Hart A., Agrawal S., Ingravallo P., Pichardo J., Kong R., Baroudy B., Malcom B., Guo Z., Prongay A., Madison V., Broske L., Cui X., Cheng K.-C., Hsieh Y., Brisson J.-M., Prelusky D., Korfmacher W., White R., Bogdanowich-Knipp S., Pavlovsky A., Bradley P., Saksena A.K., Ganguly A., Piwinski J., Girijavallabhan V., and Njoroge F.G. J. Med. Chem. 49 (2006) 6074
9. Malcom B.A., Liu R., Lahser F., Agrawal S., Belanger B., Butkiewicz N., Chase R., Gheyas F., Hart A., Hesk D., Ingravallo P., Jiang C., Kong R., Lu J., Pichardo J., Prongay A., Skelton A., Tong X., Venkatraman S., Xia E., Girijavallabhan V., and Njoroge F.G. Antimicrob. Agents Chemother. 50 (2006) 1013
10. BILN 2061 historically was the first clinical proof-of- concept HCV NS3/4A protease inhibitor discontinued due to cardiotoxicity issues in primates:. Hinrichsen H., Benhamou Y., Wedemeyer H., Reiser M., Sentjens R.E., Calleja J.L., Forns X., Erhardt A., Crönlein J., Chaves R.L., Yong C.-L., Nehmiz G., and Steinmann G. Gastroenterology 127 (2004) 1347
11. Lamarre D., Anderson P.C., Bailey M., Beaulieu P., Bolger G., Bonneau P., Bös M., Cameron D.R., Cartier M., Cordingley M.G., Faucher A.-M., Goudreau N., Kawai S.H., Kukolj G., Lagacé L., LaPlante S.R., Narjes H., Poupart M.-A., Rancourt J., Sentjens R.E., St George R., Simoneau B., Steinmann G., Thibeault D., Tsantrizos Y.S., Weldon S.M., Yong C.-L., and Llinàs-Brunet M. Nature 426 (2003) 186
12. 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., and Blatt L.M. Antimicrob. Agents Chemother. 52 (2008) 4432
13. Raboisson P., De Kock H., Rosenquist A., 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., and Simmen K. Bioorg. Med. Chem. Lett. 18 (2008) 4853
14. Manns M.P., Reesink H.W., Moreno C., Berg T., Benhamou Y., Horsmans Y.J., Dusheiko G.M., Flisiak R., Meyvisch P., Lenz O., Simmen K., and Verloes R. Hepatology 48 (2008) 1023A
15. New Clinical Data Support Broad Profile for Telaprevir in Patients with Genotype 1 Hepatitis C Virus (HCV) Infection, Vertex Press release 2008, November 1st.
16. Boceprevir Phase II Study Showed High Rate of Sustained Response With 28- and 48- Week Regimens in Genotype 1 Treatment-Naïve Hepatitis C Patients, Schering-Plough Press release 2008, November 1st.
17. 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., and Vacca J.P. J. Am. Chem. Soc. 130 (2008) 4607
18. McCauley J.A., Rudd M.T., Nguyen K.T., McIntyre C.J., Romano J.J., Bush K.J., Varga S.L., Ross III C.W., Carroll S.S., DiMuzio J., Stahlhut M.W., Olsen D.B., Lyle T.A., Vacca J.P., and Liverton N.J. Angew. Chem., Int. Ed. 47 (2008) 9104
19. McCauley, J. A.; Rudd, M. T.; McIntyre, C. J.; Nguyen, K. T.; Romano, J. J.; Butcher, J. W.; Holloway, M. K.; Wan, B.-L.; Carroll, S. S.; DiMuzio, J. M.; Graham, D. J.; Ludmerer, S. W.; Mao, S.-S.; Stahlhut, M.; Fandozzi, C.; Trainor, N.; Olsen, D. B.; Vacca, J. P.; Liverton, N. J. Abstracts of Papers, 235th ACS National Meeting, New Orleans, LA, United States, April 6-10, 2008; American Chemical Society: Washington, DC, 2008; MEDI-018.
20. Mao S.-S., DiMuzio J., McHale C., Burlein C., Olsen D., and Carroll S.S. Anal. Biochem. 373 (2008) 1
21. Lohmann V., Körner F., Koch J.-O., Herian U., Theilmann L., and Bartenschlager R. Science 285 (1999) 110
22. The protocol used was a modification of that reported in:. Migliaccio G., Tomassini J.E., Carroll S.S., Tomei L., Altamura S., Bhat B., Bartholomew L., Bosserman M.R., Ceccacci A., Colwell L.F., Cortese R., De Francesco R., Eldrup A.B., Getty K.L., Hou X.S., LaFemina R.L., Ludmerer S.W., MacCoss M., McMasters D.R., Stahlhut M.W., Olsen D.B., Hazuda D.J., and Flores O.A. J. Biol. Chem. 278 (2003) 49164
23. Narjes F., Koehler K.F., Koch U., Gerlach B., Colarusso S., Steinkühler C., Brunetti M., Altamura S., De Francesco R., and Matassa V.G. Bioorg. Med. Chem. Lett. 12 (2002) 701
24. Colarusso S., Gerlach B., Koch U., Muraglia E., Conte I., Stansfield I., Matassa V.G., and Narjes F. Bioorg. Med. Chem. Lett. 12 (2002) 705
25. Kempf D.J., Klein C., Chen H.-J., Klein L.L., Yeung C., Randolph J.T., Lau Y.Y., Chovan L.E., Guan Z., Hernandez L., Turner T.M., Dandliker P.J., and Marsh K.C. Antiviral Chem. Chemother. 18 (2007) 163
26. Chen A.-H., Lamar J., Yip Y., Victor F., Johnson R.B., Wang Q.M., Glass J.I., Heinz B., Colacino J., Guo D., Tebbe M., and Munroe J.E. Lett. Drug Des. Discovery 2 (2005) 118
27. PCT Patent (Merck & Co./IRBM): WO/08/051477 A2, May 2, 2008.
28. Dess D.B., and Martin J.C. J. Am. Chem. Soc. 113 (1991) 7277
29. The use of catalytic amounts of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) in combination with [bis(acetoxy)iodo]benzene (BAIB) as stoichiometric oxidants, as reported in:. De Mico A., Margarita R., Parlanti L., Vescovi A., and Piancatelli G. J. Org. Chem. 62 (1997) 6974 afforded the oxidation of only one of the two hydroxyamide diastereoisomers with moderate conversion.
30. The use of manganese dioxide as an heterogeneous oxidant resulted in no reaction:. Fatiadi A.J. Synthesis (1976) 65
31. The polymer-supported 2-iodylbenzamide (IBX) resulted in a sluggish reaction with only moderate conversion:. Chunk W.-J., Kim D.-K., and Lee Y.-S. Tetrahedron Lett. 44 (2003) 9251
32. Chen J.J., and Aduda V. Synth. Commun. 37 (2007) 3493
33. +, found: 682.3810.