Bulletin of the Korean Chemical Society

  • 제32권4호
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  • Pages.1146-1152
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  • 2011
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  • 0253-2964(pISSN)
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  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
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2'-Spirocyclopropyl-carbocyclic Nucleoside as a Novel Scaffold for Potent Anti-HCV Agents

  • Li, Hua (BK21-Project Team, College of Pharmacy, Chosun University) ;
  • Yoo, Jin-Cheol (BK21-Project Team, College of Pharmacy, Chosun University) ;
  • Hong, Joon-Hee (BK21-Project Team, College of Pharmacy, Chosun University)
  • 투고 : 2011.01.05
  • 심사 : 2011.01.28
  • 발행 : 2011.04.20
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초록

The discovery of 2'-spirocyclopropyl-ribocytidine (J. Med. Chem. 2010, 53, 8150-8160) as a potent inhibitor of RNA synthesis by NS5B ($IC_{50}=7.3{\mu}M$), the RNA polymerase encoded by hepatitis C Virus (HCV), has led to the synthesis and biological evaluation of several carbocyclic versions of 2'-spiropropyl-nucleosides. The cyclopentenol intermediate 7 was successfully constructed via ring-closing metathesis (RCM) from divinyl 6. Spirocyclopropanation of enone 8 was effected by using (2-chloroethyl)-dimethylsulfonium iodide and potassium tert-butoxide to form the desired intermediate 9. The synthesized nucleoside analogues 21-24 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line. Among them, the cytosine nucleoside analogue 22 exhibited significant anti-HCV activity ($EC_{50}= 8.2{\mu}M$).

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참고문헌

  1. Szabo, E.; Lotz, G.; Paska, C.; Kiss, A.; Schaff, Z. Pathol. Oncol. Res. 2003, 9, 215. https://doi.org/10.1007/BF02893380
  2. Hughes, C. A.; Shafran, S. D. Ann. Pharmacother. 2006, 40, 479. https://doi.org/10.1345/aph.1G427
  3. Chiacchio, U.; Borrello, L.; Crispino, L.; Rescifina, A.; Merino, P.; Macchi, B.; Balestrieri, E.; Mastino, A.; Piperno, A.; Romeo, G. J. Med. Chem. 2009, 52, 4054. https://doi.org/10.1021/jm900197j
  4. Gunic, E.; Chow, S.; Rong, F.; Ramasamy, K.; Raney, A.; Li, D. Y.; Huang, J.; Hamatake, R. K.; Hong, Z.; Girardet, J. L. Bioorg. Med. Chem. Lett. 2007, 17, 2456. https://doi.org/10.1016/j.bmcl.2007.02.029
  5. Koch, U.; Narjes, F. Curr. Top. Med. Chem. 2007, 7, 1302. https://doi.org/10.2174/156802607781212211
  6. Kim, H. J.; Sharon, A.; Bal, C.; Wang, J.; Allu, M.; Huang, Z.; Murray, M. G.; Bassit, L.; Schinazi, R. F.; Korba, B.; Chu, C. K. J. Med. Chem. 2009, 52, 206. https://doi.org/10.1021/jm801418v
  7. Eldrup, A. B.; Allerson, C. R.; Bennett, C. F.; Bera, S.; Bhat, B.; Bhat, N.; Bosserman, M. R.; Brooks, J.; Burlein, C.; Carrol, S. S.; Cook, P. D.; Getty, K. L.; MacCross, M.; McMasters, D. R.; Olsen, D. B.; Prakash, T. P.; Prhavc, M. Song, Q. L.; Tomassini, J. E.; Xia, J. J. Med. Chem. 2004, 47, 2283. https://doi.org/10.1021/jm030424e
  8. Clark, J. L.; Hollecker, L.; Mason, J. C.; Stuyver, L. J.; Tharnish, P. M.; Lostia, S.; McBrayer, T. R.; Schinazi, R. F.; Watanabe, K. A.; Otto, M. J.; Furman, P. A.; Stec, W. J.; Patterson, S. E.; Pankiewicz, K. W. J. Med. Chem. 2005, 48, 5504. https://doi.org/10.1021/jm0502788
  9. Jonckers, T. H.; Lin, T. I.; Buyck, C.; Lachau-Durand, S.; Vandyck, K.; Van Hoof, S.; Vandekerckhove, L. A.; Hu, L.; Berke, J. M.; Vijgen, L.; Dillen, L. L.; Cummings, M. D.; de Kock, H.; Nilsson, M.; Sund, C.; Rydegård, C.; Samuelsson, B.; Rosenquist, A.; Fanning, G.; Van Emelen, K.; Simmen, K.; Raboisson, P. J. Med. Chem. 2010, 53, 8150. https://doi.org/10.1021/jm101050a
  10. Boojamra, C. G.; Parrish, J. P.; Sperandio, D.; Gao, Y.; Petrakovsky, O. V.; Lee, S. K.; Markevich, D. Y.; Vela, J. E.; Laflamme, G.; Chen, J. M.; Ray, A. S.; Barron, A. C.; Sparacino, M. L.; Desai, M. C.; Kim, C. U.; Cihlar, T.; Mackman, R. L. Bioorg. Med. Chem. 2009, 17, 1739. https://doi.org/10.1016/j.bmc.2008.12.028
  11. Smith, D. B.; Kalayanov, G.; Sund, C.; Winqvist, A.; Maltseva, T.; Leveque, V. J.; Rajyaguru, S.; Pogam, S. L.; Najera, I.; Benkestock, K.; Zhou, X. X.; Kaiser, A. C.; Maag, H.; Cammack, N.; Martin, J. A.; Swallow, S.; Johansson, N. G.; Klumpp, K.; Smith, M. J. Med. Chem. 2009, 52, 219. https://doi.org/10.1021/jm800981y
  12. Rondla, R.; Coats, S. J.; McBrayer, T. R.; Grier, J.; Johns, M.; Tharnish, P. M.; Whitaker, T.; Zhou, L.; Schinazi, R. F. Antiviral Chem. Chemother. 2009, 20, 99. https://doi.org/10.3851/IMP1400
  13. Gosselin, G.; Griffe, L.; Meillon, J.-C.; Storer, R. Tetrahedron 2006, 62, 906. https://doi.org/10.1016/j.tet.2005.10.037
  14. Meillon, J. C.; Griffe, L.; Storer, R.; Gosselin, G. Nucleosides, Nucleotides & Nucleic Acids 2005, 24, 695. https://doi.org/10.1081/NCN-200060271
  15. Crimmins, M. T. Tetrahedron 1998, 54, 9229. https://doi.org/10.1016/S0040-4020(98)00320-2
  16. Jeong, L. S.; Lee, J. A. Antiviral Chem. Chemother. 2004, 15, 235.
  17. Ariona, O.; Gomez, A. M.; Lopez, J. C.; Plumet, J. Chemical Reviews 2007, 107, 1919. https://doi.org/10.1021/cr0203701
  18. Kim, A.; Hong, J. H. Nucleosides, Nucleotides & Nucleic Acids 2005, 24, 63. https://doi.org/10.1081/NCN-200046786
  19. Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199. https://doi.org/10.1021/cr0200872
  20. Romeo, G.; Chiacchio, U.; Corsaro, A.; Merino, P. Chem. Rev. 2010, 110, 3337. https://doi.org/10.1021/cr800464r
  21. Jeong, L. S.; Lee, J. A. Antiviral Chem. Chemother. 2004, 15, 235.
  22. Amblard, F.; Nolan, S. P.; Agrofoglio, L. A. Tetrahedron 2005, 61, 7067. https://doi.org/10.1016/j.tet.2005.04.040
  23. McReynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem. Rev. 2004, 104, 2230.
  24. Ruder, S. M.; Ronald, R. C. Tetrahedron Lett. 1984, 25, 5501. https://doi.org/10.1016/S0040-4039(01)81610-5
  25. Yin, X. Q.; Li, W. K.; Yang, M.; Schneller, S. W. Bioorg. Med. Chem. 2009, 17, 3126. https://doi.org/10.1016/j.bmc.2009.03.004
  26. Sisu, E.; Sollogoub, M.; Mallet, J. M.; Sinay, P. Tetrahedron 2002, 58, 10189. https://doi.org/10.1016/S0040-4020(02)01402-3
  27. Takaku, H.; Kamaike, K.; Tsuchiya, H. J. Org. Chem. 1984, 49, 51. https://doi.org/10.1021/jo00175a010
  28. Horita, K.; Yoshioka, T.; Tanaka, T.; Oikawa, Y.; Yonemitsu, O. Tetrahedron 1986, 42, 3021. https://doi.org/10.1016/S0040-4020(01)90593-9
  29. Oikawa, Y.; Tanaka, T.; Horita, K.; Yonemitsu, O. Tetrahedron Lett. 1984, 25, 5397. https://doi.org/10.1016/S0040-4039(01)91294-8
  30. Pathak, T.; Bazin, H. Chattopadhyaya, J. Tetrahedron 1986, 42, 5427. https://doi.org/10.1016/S0040-4020(01)82094-9
  31. Revankar, G. R.; Gupta, P. K.; Adams, A. D.; Dalley, N. K.; McKernan, P. A.; Cook, P. D.; Canonico, P. G.; Robins, R. K. J. Med Chem. 1984, 27, 1389. https://doi.org/10.1021/jm00377a002
  32. Panzica, R. P.; Rousseau, R. J.; Robins, R. K.; Townsend, L. B. J. Am. Chem. Soc. 1972, 94, 4708. https://doi.org/10.1021/ja00768a045
  33. Bonnal, C.; Chavis, C.; Lucas, M. J. Chem. Soc. Perkin Trans. 1 1994, 1401.
  34. Liu, L. J.; Hong, J. H. Nucleosides, Nucleotides & Nucleic Acids 2009, 28, 1007. https://doi.org/10.1080/15257770903362248

피인용 문헌

  1. ChemInform Abstract: 2′-Spirocyclopropyl-carbocyclic Nucleosides as a Novel Scaffold for Potent anti-HCV Agents. vol.42, pp.38, 2011, https://doi.org/10.1002/chin.201138194
  2. Efficient Synthesis of Spirocyclic Nucleosides via Michael Addition-Initiated Intermolecular Cyclopropanation Reaction vol.39, pp.11, 2011, https://doi.org/10.6023/cjoc201904074
  3. Recent progress in the synthesis of C-4′-spironucleosides and its future perspectives vol.50, pp.22, 2011, https://doi.org/10.1080/00397911.2020.1803914