Structure-Activity Relationship of Purine Ribonucleosides for Inhibition of Hepatitis C Virus RNA-Dependent RNA Polymerase

Journal of Medicinal Chemistry

Volumn 47, Issue 9, 2004, Pages 2283-2295

  Eldrup, Anne B ^a   Allerson, Charles R ^a   Bennett, C Frank ^a   Bera, Sanjib ^a   Bhat, Balkrishen ^a   Bhat, Neelima ^a   Bosserman, Michele R ^b   Brooks, Jennifer ^a   Burlein, Christine ^b   Carroll, Steven S ^b   Cook, P Dan ^a   Getty, Krista L ^b   MacCoss, Malcolm ^b   McMasters, Daniel R ^b   Olsen, David B ^b   Prakash, Thazha P ^a   Prhavc, Marija ^a   Song, Quanlai ^a   Tomassini, Joanne E ^b   Xia, Jie ^a  

^a ISIS PHARMACEUTICALS   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2' METHYLADENOSINE; 2' METHYLGUANOSINE; 2' METHYLRIBONUCLEOSIDE; ADENINE; ADENOSINE DEAMINASE; GUANINE; NS5B PROTEIN; NUCLEOSIDE; NUCLEOSIDE ANALOG; NUCLEOSIDE TRIPHOSPHATE; PURINE NUCLEOSIDE PHOSPHORYLASE; RNA DIRECTED RNA POLYMERASE; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME METABOLISM; HEPATITIS C VIRUS; IN VITRO STUDY; PHARMACOPHORE; REPLICON; RNA REPLICATION; RNA SYNTHESIS; STEREOCHEMISTRY; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION; VIRUS INHIBITION; VIRUS REPLICATION;

EID: 11144355286     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030424e     Document Type: Article

References (32)

1. Hwang, S. B.; Park, K.-J.; Kim, Y.-S.; Sung, Y. C.; Lai, M. M. C. Hepatitis C virus NS5B protein is a membrane-associated phosphoprotein with a predominantly perinuclear localization. Virology 1997, 227, 439-446.
2. Behrens, S.-E.; Tomei, L.; De Francesco, R. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J. 1996, 15, 12-22.
3. Takamizawa, A.; Mori, C.; Fuke, I.; Manabe, S.; Murakami, S.; Fujita, J. ; Onishi, E.; Andoh, T.; Yoshida, I.; Okayama, H. Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol. 1991, 65, 1105-1113.
4. Colarusso, S.; Gerlach, B.; Koch, U.; Muraglia, E.; Conte, I.; Stansfield, I.; Matassa, V. G.; Narjes, F. Evolution, synthesis and SAR of tripeptide α-ketoacid inhibitors of the hepatitis C virus NS3/NS4A serine protease. Bioorg. Med. Chem. Lett. 2002, 12, 705-708.
5. Narjes, F.; Koehler, K. F.; Koch, U.; Gerlach, B.; Colarusso, S.; Steinkuhler, C.; Brunetti, M.; Altamura, S.; De Francesco, R.; Matassa, V. G. A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease. Bioorg. Med. Chem. Lett. 2002, 12, 701-704.
6. Steinkuhler, C.; Koch, U.; Narjes, F.; Matassa, V. G. Hepatitis C virus serine protease inhibitors: current progress and future challenges. Curr. Med. Chem. 2001, 8, 919-932.
7. Llinas-Brunet, M.; Bailey, M.; Fazal, G.; Goulet, S.; Halmos, T.; Laplante, S.; Maurice, R.; Poirier, M.; Poupart, M.-A.; Thibeault, D.; Wernic, D.; Lamarre, D. Peptide-based inhibitors of the hepatitis C virus serine protease. Bioorg. Med. Chem. Lett. 1998, 8, 1713-1718.
8. Llinas-Brunet, M.; Bailey, M.; Deziel, R.; Fazal, G.; Gorys, V.; Goulet, S.; Halmos, T.; Maurice, R.; Poirier, M.; Poupart, M.-A.; Rancourt, J.; Thibeault, D.; Wernic, D.; Lamarre, D. Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus senne serine protease. Bioorg. Med. Chem. Lett. 1998, 8, 2719-2724.
9. Lamarre, D.; Anderson, P. C.; Balley, M.; Beaulieu, P.; Bolger, G.; Bonneau, P.; Bos, M.; Cameron, D. R.; Cartier, M.; Cordingley, M. G.; Faucher A.-M.; Goudreau, N.; Kawai, S. H.; Kukolj, G.; Lagacé, I.; Laplante, S. R.; Narjes, H.; Poupart, M.-A.; Rancourt, G.; Sentjens, R. E.; St. George, R.; Simoneau, B.; Stelnmann, G.; Thibeault, D.; Tsantrzos, Y. S.; Weldon, S. M.; Yong, C.-L.; Llinas-Brunet, M. Nature 2003, 426, 186-189.
10. Chan, L.; Reddy, T. J.; Proulx, M.; Das, S. K.; Pereira, O.; Wang, W.; Siddiqui, A.; Yannopoulos, C. G.; Poisson, C.; Turcotte, N.; Drouin, A.; Alaoui-Ismaili, M. H.; Bethell, R.; Hamel, M.; L'Heureux, L.; Bilimoria, D.; Nguyen-Ba, N. Identification of N,N-Disubstituted Phenylalanines as a Novel Class of Inhibitors of Hepatitis C NS5B Polymerase. J. Med. Chem. 2003, 46, 1283-1285.
11. Wang, M.; Ng, K. K. S.; Cherney, M. M.; Chan, L.; Yannopoulos, C. G.; Bedard, J.; Morin, N.; Nguyen-Ba, N.; Alaoui-Ismaili, M. H.; Bethell, R. C.; James, M. N. G. Non-nucleoside Analogue Inhibitors Bind to an Allosteric Site on HCV NS5B Polymerase. J. Biol. Chem. 2003, 278, 9489-9495.
12. Dhanak, D.; Duffy, K. J.; Johnston, V. K.; Lin-Goerke, J.; Darcy, M.; Shaw, A. N.; Gu, B.; Silverman, C.; Gates, A. T.; Nonnemacher, M. R.; Earnshaw, D. L.; Casper, D. J.; Kaura, A.; Baker, A.; Greenwood, C.; Gutshall, L. L.; Maley, D.; DelVecchio, A.; Macarron, R.; Hofmann, G. A.; Alnoah, Z.; Cheng, H.-Y.; Chan, G.; Khandekar, S.; Keenan, R. M.; Sarisky, R. T. Identification and Biological Characterization of Heterocyclic Inhibitors of the Hepatitis C Virus RNA-Dependent RNA Polymerase. J. Biol. Chem. 2002, 277, 38322-38327.
13. Gu, B.; Johnston, V. K.; Gutshall, L. L.; Nguyen, T. T.; Gontarek, R. R. ; Darcy, M. G.; Tedesco, R.; Dhanak, D.; Duffy, K. J.; Kao, C. C.; Sarisky, R. T. Arresting Initiation of Hepatitis C Virus RNA Synthesis Using Heterocyclic Derivatives. J. Biol. Chem. 2003, 278, 16602-16607.
14. Carroll, S. S.; Tomassini, J. E.; Bosserman, M.; Getty, K.; Stahlhut, M. W.; Eldrup, A. B.; Bhat, B.; Hall, D.; Simcoe, A. L.; LaFemina, R.; Rutkowski, C. A.; Wolanski, B.; Yang, Z.; Migliaccio, G.; De Francesco, R.; Kuo, L. C.; MacCoss, M.; Olsen, D. B. Inhibition of Hepatitis C Virus RNA Replication by 2′-Modified Nucleoside Analogs. J. Biol. Chem. 2003, 278, 11979-11984.
15. Shim, J.; Larson, G.; Lai, V.; Naim, S.; Wu, J. Z. Canonical 3′-deoxyribonucleotides as chainterminator for HCV NS5B RNA-dependent RNA polymerase. Antiviral Res. 2003, 243-251.
16. Migliaccio, G.; Tomassini, J. E.; Carroll, S. S.; Tomei, L.; Altamura, S.; Bhat, B.; Bartholomew, L.; Bosserman, M.; Ceccacci, A.; Colwell, L. F.; Cortese, R.; De Francesco, R.; Eldrup, A. B.; Getty, K.; Hou, W. S.; LaFemina, R.; Ludmere, S. W.; MacCoss, M.; MacMasters, D. R.; Stahlhut, M. W.; Olsen, D. B.; Hazuda, D. J.; Flores, O. Identification and validation of ribonucleoside analogues as hepatitis C antiviral agents. J. Biol. Chem. 2003, 278, 49164-49170.
17. Crotty, S.; Cameron, C. E.; Andino, R. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 6895-6900.
18. Pankiewicz, K. W.; Krzeminski, J.; Watanabe, K. A. Nucleosides. 164. Studies directed toward the synthesis of 2′-deoxy-2′-substituted arabino nucleosides. 10. Synthesis of 2′-β-fluoro- and 3′-a-fluoro-substituted guanine nucleosides. Effect of sugar conformational shifts on nucleophilic displacement of the 2′-hydroxy and 3′-hydroxy group with DAST. J. Org. Chem. 1992, 57, 7315-7321.
19. Kawasaki, A. M.; Casper, M. D.; Freier, S. M.; Lesnik, E. A.; Zounes, M. C.; Cummins, L. L.; Gonzalez, C.; Cook, P. D. Uniformly modified 2′-deoxy-2′-fluoro phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets. J. Med. Chem. 1993, 36, 831-841.
20. Franchetti, P.; Cappellacci, L.; Marchetti, S.; Trincavelli, L.; Martini, C.; Mazzoni, M. R.; Lucacchini, A.; Grifantini, M. 2′-C-Methyl Analogs of Selective Adenosine Receptor Agonists: Synthesis and Binding Studies. J. Med. Chem. 1998, 41, 1708-1715.
21. Harry-O'kuru, R. E.; Smith, J. M.; Wolfe, M. S. A Short, Flexible Route toward 2′-C-Branched Ribonucleosides. J. Org. Chem. 1997, 62, 1754-1759.
22. Samano, V.; Robins, M. J. Nucleic acid related compounds. 60. Mild periodinane oxidation of protected nucleosides to give 2′- and 3′-ketonucleosides. The first isolation of a purine 2′ -deoxy-3′-ketonucleoside derivative. J. Org. Chem. 1990, 55, 5186-5188.
23. Markiewicz, W. T.; Wiewiorowski, M. A new type of silyl protecting groups in nucleoside chemistry. Nucleic Acids Res., Spec. Publ. 1978, 4, 185-188.
24. Schmit, C.; Bevierre, M.-O.; De Mesmaeker, A.; Altmann, K.-H. The effects of 2′- and 3′-alkyl substituents on oligonucleotide hybridization and stability. Bioorg. Med. Chem. Lett. 1994, 4, 1969-1974.
25. Koole, L. H.; Buck, H. M.; Vial, J. M.; Chattopadhyaya, J. Synthesis and conformation of 9-(3′-C-methyl-β-D-xylo-furanosyl)adenine and 3′-C-methyladenosine, two sugar-methylated nucleoside analogs. Acta Chem. Scand. 1989, 43, 665-669.
26. Carroll, S. S.; Lafemina, R. L.; Hall, D. L.; Himmelberger, A. L.; Kuo, L. C.; Maccoss, M.; Olsen, D. B.; Rutkowski, C. A.; Tomassini, J. E.; An, H.; Bhat, B.; Bhat, N.; Cook, P. D.; Eldrup, A. B.; Guinosso, C. J.; Prhavc, M.; Prakash, T. P. Preparation of nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase. PCT Int. Appl. WO 02/57425, 2002; 235 pp.
27. Carroll, S. S.; Maccoss, M.; Olsen, D. B.; Bhat, B.; Bhat, N.; Cook, P. D.; Eldrup, A. B.; Prakash, T. P.; Prhavc, M.; Song, Q. Preparation of nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase. PCT Int. Appl. WO 02/57287, 2002; 85 pp.
28. Plavec, J.; Tong, W.; Chattopadhyaya, J. How do the gauche and anomeric effects drive the pseudorotational equilibrium of the pentofuranose moiety of nucleosides? J. Am. Chem. Soc. 1993, 115, 9734-9746.
29. Ford, H., Jr.; Dai, F.; Mu, L.; Siddiqui, M. A.; Nicklaus, M. C.; Anderson, L.; Marquez, V. E.; Barchi, J. J. Adenosine Deaminase Prefers a Distinct Sugar Ring Conformation for Binding and Catalysis: Kinetic and Structural Studies. Biochemistry 2000, 39, 2581-2592.
30. Seela, F.; Muth, H. P.; Bindig, U. Synthesis of 6-substituted 7-carbapurine 2′,3′-dideoxynucleosides. Solid-liquid phase-transfer glycosylation of 4-chloropyrrolo[2,3-d]pyrimidine and deoxygenation of its 2′-deoxyribofuranoside. Synthesis 1988, 670-674.
31. Kearsley, S. K. Unpublished in-house distance geometry program. In Distance Geometry and Molecular Conformation, 2nd ed.; Crippen, C. M., Havel, T. F. Eds.; Research Studio Press, Wiley: New York.
32. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel-an integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J. Comput. Chem. 1990, 11, 440-467.