P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 2, 2010, Pages 567-570

  Nair, Latha G ^a   Sannigrahi, Mousumi ^a   Bogen, Stephane ^a   Pinto, Patrick ^a   Chen, Kevin X ^a   Prongay, Andrew ^a   Tong, Xiao ^a   Cheng, K C ^a   Girijavallabhan, Viyyoor ^a   George Njoroge, F ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Amides; HCV protease; Lactams

Indexed keywords

AMIDE; BOCEPREVIR; LACTAM; NS3 PROTEASE; PROTEINASE INHIBITOR; TELAPREVIR; UNCLASSIFIED DRUG;

AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG POTENCY; HEPATITIS C VIRUS; HUMAN; NONHUMAN; PHASE 3 CLINICAL TRIAL; RAT; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

AMIDES; ANIMALS; ANTIVIRAL AGENTS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; LACTAMS; OLIGOPEPTIDES; PROLINE; PROTEASE INHIBITORS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; VIRAL NONSTRUCTURAL PROTEINS;

HEPATITIS C VIRUS; RATTUS;

EID: 72249116288     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.11.094     Document Type: Article

References (45)

1. Cohen J. Science 285 (1999) 26
2. Alter M.J., Kruszon-Moran D., Nainan O.V., McQuillan G.M., Gao F., Moyer L.A., Kaslow R.A., and Margolis H.S. N. Eng. J. Med. 341 (1999) 556
3. Cuthbert J.A. Clin. Microbiol. Rev. 7 (1994) 505
4. Monto A., and Wright T.L. Semin. Oncol. (2001) 441
5. Neumann A.U., Lam N.P., Dahari H., Gretch D.R., Wiley T.E., Layden T.J., and Perelson A.S. Science 282 (1998) 103
6. Rosen H.R., and Gretch D.R. Mol. Med. Today 5 (1999) 393
7. Di Bisceglie A.M., McHutchison J., and Rice C.M. Hepatology 35 (2002) 224
8. Lindenbach B.D., and Rice C.M. Nature 436 (2005) 933
9. Kolykhalov A.A., Mihalik K., Feinstone S.M., and Rice C.M. J. Virol. 74 (2000) 2046
10. Lesk A.M., and Fordham W.D. J. Mol. Biol. 258 (1996) 501
11. DeFrancesco R., and Steinkuhler C. Curr. Top. Microbiol. Immunol. 242 (2000) 149
12. Yan Y., Li Y., Munshi S., Sardana V., Cole J.L., Sardana M., Steinkuehler C., Tomei L., De Francesco R., Kuo L.C., and Chen Z. Protein Sci. 7 (1998) 837
13. Di Marco S., Rizzi M., Volpari C., Walsh M.A., Narjes F., Colarusso S., De Francesco R., Matassa V.G., and Sollazzo M. J. Biol. Chem. 275 (2000) 7152
14. De Francesco R., and Migliaccio G. Nature 436 (2005) 953
15. Tan S.-L., He Y., Huang Y., and Gale Jr. M. Curr. Opin. Pharmacol. 4 (2004) 465
16. Malancona S., Colarrusso S., Ontoria J.M., Marchetti A., Poma M., Stansfield I., Laufer R., Marco A.D., Taliani M., Verdirame M., Gonzalez-paz O., Matassa V.G., and Narjes F. Bioorg. Med. Chem. Lett. 14 (2004) 4575
17. Llinas-Brunet M., Bailey M.D., Ghiro E., Gorys V., Halmos T., Poirier M., Rancourt J., and Goudreau N. J. Med. Chem. 47 (2004) 6584
18. Andrews D.M., Barnes M.C., Dowle M.D., Hind S.L., Johnson M.R., Jones P.S., Mills G., Patikis A., Pateman T.J., Redfern T.J., Ed Robinson J., Slater M.J., and Trivedi. Org. Lett. 5 (2003) 4631
19. Zhang X. Idrugs 5 (2002) 154
20. Dymock B.W. Exp. Opin. Emerg. Drugs 6 (2001) 13
21. Dymock B.W., Jones P.S., and Wilson F.X. Antiviral. Chem. Chemother. 11 (2000) 79
22. Zhang R., Durkin J.P., and Windsor W.T. Bioorg. Med. Chem. Lett. 12 (2002) 1005
23. Ingallinella P., Fattori D., Altamura S., Steinkuhler C., Koch U., Cicero D., Bazzo R., Cortese R., Bianchi E., and Pessi A. Biochemistry 41 (2002) 5483
24. Beevers R., Carr M.G., Jones P.S., Jordan S., Kay P.B., Lazell R.C., and Raynham T.M. Bioorg. Med. Chem. Lett. 12 (2002) 641
25. For BILN-2061, see:. 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., George T.S., Simoneau B., Steinmann G., Thibeault D., Tsantrizos Y.S., Weldon S.M., Yong C.-L., and Llinàs-Brunet M. Nature 426 (2003) 186
26. Tsantrizos Y.S., Bolger G., Bonneau P., Cameron D.R., Gordreau N., Kukolj G., LaPlante S.R., Llinas-Brunet M., Nar H., and Lamarre D. Angew. Chem., Int. Ed. 42 (2003) 1355
27. For VX-950, see:. Yip Y., Victor F., Lamar J., Johnson R., Wang Q., May G., John I., Yumibe N., Wakulchik M., Munroe J., and Chen S.-H. Bioorg. Med. Chem. Lett. 14 (2004) 5007
28. Perni, R. Gordon Research Conference, New London, New Hampshire, 2005, August 7-12.
29. MK-7009 references:. Anon. Nat. Rev. Drug Disc. 8 (2009) 11
30. Harper S., Ferrara M., Crescenzi B., Pompei M., Palumbi M.C., DiMuzio J.M., Donghi M., Fiore F., Koch U., Liverton N.J., Pesci S., Petrocchi A., Rowley M., Summa V., and Gardelli C. J. Med. Chem. 52 (2009) 4820
31. For Boceprevir:. Venkatraman S., Bogen S., Arasappan A., Bennet F., Chen K., Jao E., Liu Y.-T., Lovey R., Hendreta 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., Malcolm B., Guo Z., Prongay A., Madison V., Broske L., Cui X., Cheng K.-C., Hsieh T.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
32. Zhang R., and Madalengoitia J.S. J. Org. Chem. 64 (1999) 330
33. Chen K.X., Arasappan A., Njoroge F.G., Vibulbhan B., Buevich A., Chan T.-M., and Girijavallabhan V. J. Org. Chem. 67 (2002) 2730
34. Arasappan A., Chen K.X., Njoroge F.G., Parekh T.N., and Girijavallabhan V. J. Org. Chem. 67 (2002) 3923
35. Sannigrhi M., Pinto P., Chan T.M., Shih N.-Y., and Njoroge F.G. Tetrahedron Lett. 47 (2006) 4877
36. Zhang R., Beyer B.M., Durkin J., Ingram R., Njoroge F.G., Windsor W.T., and Malcolm B.A. Anal. Biochem. 270 (1999) 268
37. Taremi S.S., Beyer B., Maher M., Yao N., Prosise W., Weber P.C., and Malcolm B.A. Protein Sci. 7 (1998) 2143
38. * and discussions, see: Morrison, J. F.; Walsh, C. T. In Adv. Enzymol., Meister, A., Ed.; Interscience: NY, 1988; Vol. 61, pp 201-301.
39. Chung V., Carroll A.R., Gray N.M., Parry N.R., Thommes P.A., Viner K.C., and D'Souza E.A. Antimicrob. Agents Chemother. 49 (2005) 1381
40. Blight K.J., Kolykhalov A.A., and Rice C.M. Science 290 (2000) 1972
41. Lohmann V., Körner F., Koch J.-O., Herian U., Theilmann L., and Bartenschlager R. Science 285 (1999) 110
42. For other P4 SAR reported from our reserach see:. Venkatraman S., Blackman M., Wu W., Nair L., Arasappan A., Padilla A., Bogen S., Bennett F., Chen K., Pichardo J., Tong X., Prongay A., Cheng K.-C., Girijavallabhan V., and George N.F. Bioorg. Med. Chem. 17 (2009) 4486
43. Bogen S.L., Pan W., Ruan S., Nair L.G., Arasappan A., Bennett F., Chen K.X., Jao E., Venkatraman S., Vibulbhan B., Liu R., Cheng K.-C., Guo Z., Tong X., Saksena A.K., Girijavallabhan V., and Njoroge F.G. J. Med. Chem. 52 (2009) 3679
44. Chen K.X., Nair L., Vibulbhan B., Yang W., Arasappan A., Bogen S.L., Venkatraman S., Bennett F., Pan W., Blackman M.L., Padilla A.I., Prongay A., Cheng K.-C., Tong X., Shih N.-Y., and Njoroge F.G. J. Med. Chem. 52 (2009) 1370
45. X-ray crystal coordinates are deposited in the Protein Data Bank and the PDB number is 3KN2.