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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 方俊民(Jim-Min Fang) | |
| dc.contributor.author | Yu-Cheng Liu | en |
| dc.contributor.author | 劉宥承 | zh_TW |
| dc.date.accessioned | 2021-06-16T08:47:57Z | - |
| dc.date.available | 2018-09-02 | |
| dc.date.copyright | 2013-09-02 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-20 | |
| dc.identifier.citation | 1. WHO
http://www.who.int/influenza/human_animal_interface/faq_H7N9/en/index.html. 2. De Clerq, E. Nat. Rev. Drug Discov. 2006, 5, 1015–1025. Antiviral agents against influenza A viruses. 3. Suzuki, Y. Biol. Pharm. Bull. 2005, 28, 399–408. Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. 4. Horimoto, T.; Kawaoka, Y. Nat. Rev. Microbiol. 2005, 3, 591–600. Influenza: lessons from past pandemics, warnings from current incidents. 5. Tong, S.; Li, Y.; Rivailler, P.; Conrardy, C.; Castillo, D. A.; Chen, L. M.; Recuenco, S.; Ellison, J. A.; Davis, C. T.; York, I. A.; Turmelle, A. S.; Moran, D.; Rogers, S.; Shi, M.; Tao, Y.; Weil, M. R.; Tang, K.; Rowe, L. A.; Sammons, S.; Xu, X.; Frace, M.; Lindblade, K. A.; Cox, N. J.; Anderson, L. J.; Rupprecht, C. E.; Donis, R. O. 108 Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 4269–4274. A distinct lineage of influenza A virus from bats. 6. Das, K.; Aramini, J. M.; Ma, L.-C.; Krug, R. M.; Arnold, E. Nat. Struct. Mol. Biol. 2010, 17, 530–538. Structures of influenza A proteins and insights into antiviral drug targets. 7. Wilson, I. A.; Skehel, J. J.; Wiley, D. C. Nature 1981, 289, 366–373. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. 8. Weis, W.; Brown, J. H.; Cusack, S.; Paulson, J. C.; Skehel, J. J.; Wiley, D. C. Nature 1988, 333, 426–431. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. 9. Varghese, J. N.; Laver, W. G.; Colman, P. M. Nature 1983, 303, 35–40. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. 10. (a) Holsinger, L. J.; Nichani, D.; Pinto, L. H.; Lamb, R. A. J. Virol. 1994, 68, 1551– 1563. Influenza A virus M2 ion channel protein: a structure-functionAnalysis; (b) Kozakov, D.; Chuang, G. Y.; Beglov, D.; Vajda, S. Trends Biochem. Sci. 2010, 35, 109 471–475. Where does amantadine bind to the influenza virus M2 proton channel? 11. Schnell, J. R.; Chou, J. J. Nature 2008, 451, 591–595. Structure and mechanism of the M2 proton channel of influenza A virus. 12. (a) Bright, R. A.; Medina, M.-j.; Xu, X.; Perez-Oronoz, G.; Wallis, T. R.; Davis, X. M.; Povinelli, L.; Cox, N. J.; Klimov, A. I. The Lancet 2005, 366, 1175–1181. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern; (b) Bright, R. A.; Shay, D. K.; Shu, B.; Cox, N. J.; Klimov, A. I. J. Am. Med. Assoc. 2006, 295, 891–894. Adamantane resistance among influenza A viruses isolated early during the 2005– 2006 influenza season in the United States. 13. (a) Pielak, R. M.; Schnell, J. R.; Chou, J. J. Proc. Natl. Acad. Sci. U .S. A. 2009, 106, 7379–7384. Mechanism of drug inhibition and drug resistance of influenza A M2 channel; (b) Jing, X.; Ma, C.; Ohigashi, Y.; Oliveira, F. A.; Jardetzky, T. S.; Pinto, L. H.; Lamb, R. A. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 10967–10972. Functional studies indicate amantadine binds to the pore of the influenza A virus 110 M2 proton-selective ion channel. 14. Cady, S. D.; Schmidt-Rohr, K.; Wang, J.; Soto, C. S.; DeGrado, W. F.; Hong, M. Nature 2010, 463, 689–692. Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers. 15. Guo, C.-T.; Sun, X.-L.; Kanie, O.; Shortridge, K. F.; Suzuki, T.; Miyamoto, D.; Hidari, K. I.-P. J.; Wong, C.-H.; Suzuki, Y. Glycobiology 2002, 12, 183–190. An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses. 16. Bodian, D. L.; Yamasaki, R. B.; Buswell, R. L.; Stearns, J. F.; White, J. M.; Kuntz, I. D. Biochemistry 1993, 32, 2967–2978. Inhibition of the fusion-inducing conformational change of influenza hemagglutinin by benzoquinones and hydroquinones. 17. Russell, R. J.; Kerry, P. S.; Stevens, D. J.; Steinhauer, D. A.; Martin, S. R.; Gamblin, S. J.; Skehel, J. J. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 17736–17741. Structure of influenza hemagglutinin in complex with an inhibitor of membrane 111 fusion. 18. Taylor, N. R.; von Itzstein, M. J. Med. Chem. 1994, 37, 616–624. Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. 19. Chong, A. K.; Pegg, M. S.; Taylor, N. R.; von Itzstein, M. Eur. J. Biochem. 1992, 207, 335–343. Evidence for a sialosyl cation transition-state complex in the reaction of sialidase from influenza virus. 20. Meindl, P.; Bodo, G.; Palese, P.; Schulman, J.; Tuppy, H. Virology 1974, 58, 457– 463. Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 21. von Itzstein, M. Nat. Rev. Drug. Discov. 2007, 6, 967–974. The war against influenza: discovery and development of sialidase inhibitors. 22. Bossart-Whitaker, P.; Carson, M.; Babu, Y. S.; Smith, C. D.; Laver, W. G.; Air, G. M. J. Mol. Biol. 1993, 232, 1069–1083. Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 112 2,3-dehydro-N-acetyl neuraminic acid. 23. von Itzstein, M.; Wu, W. Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Van Phan, T.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Vardhese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R. Nature 1993, 363, 418–423. Rational design of potent sialidase-based inhibitors of influenza virus replication. 24. Holzer, C. T.; von Itzstein, M.; Jin, B.; Pegg, M. S.; Stewart, W. P.; Wu, W. Y., Glycoconj. J. 1993, 10, 40–44. Inhibition of sialidases from viral, bacterial and mammalian sources by analogues of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid modified at the C-4 position. 25. Woods, J. M.; Bethell, R. C.; Coates, J. A.; Healy, N.; Hiscox, S. A.; Pearson, B. A.; Ryan, D. M.; Ticehurst, J.; Tilling, J.; Walcott, S. M. Antimicrob. Agents Chemother. 1993, 37, 1473–1479. 4-Guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of 113 influenza A and B viruses in vitro. 26. (a) Ryan, D. M.; Ticehurst, J.; Dempsey, M. H.; Penn, C. R. Antimicrob. Agents Chemother. 1994, 38, 2270–2275. Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is consistent with extracellular activity of viral neuraminidase (sialidase); (b) Dunn, C. J.; Goa, K. L. Drugs 1999, 58, 761–784. Zanamivir: a review of its use in influenza; (c) Elliott, M. Philos. Trans. Royal Soc. B: Biol. Sci. 2001, 356, 1885– 1893. Zanamivir: from drug design to the clinic. 27. Andrews, D. M.; Cherry, P. C.; Humber, D. C.; Jones, P. S.; Keeling, S. P.; Martin, P. F.; Shaw, C. D.; Swanson, S. Eur. J. Med. Chem. 1999, 34, 563–574. Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-guanidino-Neu5Ac2en (zanamivir) modified in the glycerol side-chain. 28. Honda, T.; Masuda, T.; Yoshida, S.; Arai, M.; Kobayashi, Y.; Yamashita, M. Bioorg. Med. Chem. Lett. 2002, 12, 1921–1924. Synthesis and anti-influenza virus activity of 4-guanidino-7-substituted Neu5Ac2en derivatives. 114 29. Honda, T.; Masuda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Bioorg. Med. Chem. Lett. 2002, 12, 1925–1928. Synthesis and anti-Influenza virus activity of 7-O-alkylated derivatives related to zanamivir. 30. Liu, Z.-y.; Wang, B.; Zhao, L.-x.; Li, Y.-h.; Shao, H.-y.; Yi, H.; You, X.-f.; Li, Z.-r. Bioorg. Med. Chem. Lett. 2007, 17, 4851–4854. Synthesis and anti-influenza activities of carboxyl alkoxyalkyl esters of 4-guanidino-Neu5Ac2en (zanamivir). 31. Honda, T.; Kubo, S.; Masuda, T.; Arai, M.; Kobayashi, Y.; Yamashita, M. Bioorg. Med. Chem. Lett. 2009, 19, 2938–2940. Synthesis and in vivo influenza virus-inhibitory effect of ester prodrug of 4-guanidino-7-O-methyl-Neu5Ac2en. 32. Kubo, S.; Tomozawa, T.; Kakuta, M.; Tokumitsu, A.; Yamashita, M. Antimicrob. Agents Chemother. 2010, 54, 1256–1264. Laninamivir prodrug CS-8958, a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration. 33. Ishizuka, H.; Yoshiba, S.; Okabe, H.; Yoshihara, K. J. Clin. Pharmacol. 2010, 50, 1319–1329. Clinical pharmacokinetics of laninamivir, a novel long-acting 115 neuraminidase inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in healthy male volunteers. 34. (a) Watson, K. G.; Cameron, R.; Fenton, R. J.; Gower, D.; Hamilton, S.; Jin, B.; Krippner, G. Y.; Luttick, A.; McConnell, D.; MacDonald, S. J. F.; Mason, A. M.; Nguyen, V.; Tucker, S. P.; Wu, W.-Y. Bioorg. Med. Chem. Lett. 2004, 14, 1589– 1592. Highly potent and long-acting trimeric and tetrameric inhibitors of influenza virus neuraminidase; (b) Macdonald, S. J.; Watson, K. G.; Cameron, R.; Chalmers, D. K.; Demaine, D. A.; Fenton, R. J.; Gower, D.; Hamblin, J. N.; Hamilton, S.; Hart, G. J.; Inglis, G. G.; Jin, B.; Jones, H. T.; McConnell, D. B.; Mason, A. M.; Nguyen, V.; Owens, I. J.; Parry, N.; Reece, P. A.; Shanahan, S. E.; Smith, D.; Wu, W. Y.; Tucker, S. P. Antimicrob. Agents Chemother. 2004, 48, 4542–4549. Potent and long-acting dimeric inhibitors of influenza virus neuraminidase are effective at a once-weekly dosing regimen. 35. Macdonald, S. J. F.; Cameron, R.; Demaine, D. A.; Fenton, R. J.; Foster, G.; Gower, D.; Hamblin, J. N.; Hamilton, S.; Hart, G. J.; Hill, A. P.; Inglis, G. G. A.; Jin, B.; 116 Jones, H. T.; McConnell, D. B.; McKimm-Breschkin, J.; Mills, G.; Nguyen, V.; Owens, I. J.; Parry, N.; Shanahan, S. E.; Smith, D.; Watson, K. G.; Wu, W.-Y.; Tucker, S. P. J. Med. Chem. 2005, 48, 2964–2971. Dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including H5N1 avian influenza. 36. Kim, C. U.; Lew, W.; Williams, M. A.; Liu, H.; Zhang, L.; Swaminathan, S.; Bischofberger, N.; Chen, M. S.; Mendel, D. B.; Tai, C. Y.; Laver, W. G.; Stevens, R. C. J. Am. Chem. Soc. 1997, 119, 681–690. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. 37. Kim, C. U.; Lew, W.; Williams, M. A.; Wu, H.; Zhang, L.; Chen, X.; Escarpe, P. A.; Mendel, D. B.; Laver, W. G.; Stevens, R. C. J. Med. Chem. 1998, 41, 2451–2460. Structure−activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors. 117 38. (a) Li, W.; Escarpe, P. A.; Eisenberg, E. J.; Cundy, K. C.; Sweet, C.; Jakeman, K. J.; Merson, J.; Lew, W.; Williams, M.; Zhang, L.; Kim, C. U.; Bischofberger, N.; Chen, M. S.; Mendel, D. B. Antimicrob. Agents Chemother. 1998, 42, 647–653. Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071; (b) Sidwell, R. W.; Huffman, J. H.; Barnard, D. L.; Bailey, K. W.; Wong, M. H.; Morrison, A.; Syndergaard, T.; Kim, C. U. Antiviral Res. 1998, 37, 107–120. Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. 39. Sweeny, D. J.; Lynch, G.; Bidgood, A. M.; Lew, W.; Wang, K. Y.; Cundy, K. C. Drug Metab. Dispos. 2000, 28, 737–741. Metabolism of the influenza neuraminidase inhibitor prodrug oseltamivir in the rat. 40. Yamamoto, T.; Kumazawa, H.; Inami, K.; Teshima, T.; Shiba, T. Tetrahedron Lett. 1992, 33, 5791–5794. Syntheses of sialic acid isomers with inhibitory activity against neuraminidase. 41. Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, 118 T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. L.; Laver, G. W.; Montgomery, J. A. J. Med. Chem. 2000, 43, 3482–3486. BCX-1812 (RWJ-270201): discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design. 42. Sidwell, R. W.; Smee, D. F.; Huffman, J. H.; Barnard, D. L.; Bailey, K. W.; Morrey, J. D.; Babu, Y. S. Antimicrob. Agents Chemother. 2001, 45, 749–757. In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RJW-270201. 43. Gubareva, L. V.; Webster, R. G.; Hayden, F. G. Antimicrob. Agents Chemother. 2001, 45, 3403–3408. Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. 44. de Jong, M. D.; Tran, T. T.; Truong, H. K.; Vo, M. H.; Smith, G. J.; Nguyen, V. C.; Bach, V. C.; Phan, T. Q.; Do, Q. H.; Guan, Y.; Peiris, J. S.; Tran, T. H.; Farrar, J. N. Engl. J. Med. 2005, 353, 2667–2672. Oseltamivir resistance during treatment of 119 influenza A (H5N1) infection. 45. Dharan, N. J.; Gubareva, L. V.; Meyer, J. J.; Okomo-Adhiambo, M.; McClinton, R. C.; Marshall, S. A.; St George, K.; Epperson, S.; Brammer, L.; Klimov, A. I.; Bresee, J. S.; Fry, A. M. J. Am. Med. Assoc. 2009, 301, 1034–1041. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. 46. Collins, P. J.; Haire, L. F.; Lin, Y. P.; Liu, J.; Russell, R. J.; Walker, P. A.; Skehel, J. J.; Martin, S. R.; Hay, A. J.; Gamblin, S. J. Nature 2008, 453, 1258–1261. Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants. 47. Shie, J. J.; Fang, J. M.; Wang, S. Y.; Tsai, K. C.; Cheng, Y. S.; Yang, A. S.; Hsiao, S. C.; Su, C. Y.; Wong, C. H. J. Am. Chem. Soc. 2007, 129, 11892–11893. Synthesis of tamiflu and its phosphonate congeners possessing potent anti-influenza activity. 48. Clark, C. H.; Gutierrez, G. Am. J. Crit. Care. 1992, 1, 53–60. Gastric intramucosal pH: a noninvasive method for the indirect measurement of tissue oxygenation. 120 49. (a) Vane, J. R., J. Physiol. Pharmacol. 2000, 51, 573–586. The fight against rheumatism: from willow bark to COX-1 sparing drugs; (b) Rao, P. P. N.; Kabir, S. N.; Mohamed, T. Pharmaceuticals 2010, 3, 1530–1549. Nonsteroidal anti-inflammatory drugs (NSAIDs): progress in small molecule drug development. 50. (a) Vane, J. R. Nat. New Biol. 1971, 231, 232–235. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs; (b) Smith, J. B.; Willis, A. L. Nat. New Biol. 1971, 231, 235-237. Aspirin selectively inhibits prostaglandin production in human platelets. 51. (a) Vane, J. R.; Botting, R. M. Thromb. Res. 2003, 110, 255–258. The mechanism of action of aspirin; (b) Rosen, G. D.; Birkenmeier, T. M.; Raz, A.; Holtzman, M. J. Biochem. Biophys. Res. Commun. 1989, 164, 1358–1365. Identification of a cyclooxygenase-related gene and its potential role in prostaglandin formation. 52. Serhan, C. N.; Chiang, N.; Van Dyke, T. E. Nat. Rev. Immunol. 2008, 8, 349-361. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. 53. Mitchell, J. A.; Akarasereenont, P.; Thiemermann, C.; Flower, R. J.; Vane, J. R., 121 Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 11693–11697. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. 54. Luong, C.; Miller, A.; Barnett, J.; Chow, J.; Ramesha, C.; Browner, M. F. Nat. Struct. Biol. 1996, 3, 927–933. Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2. 55. Kurumbail, R. G.; Stevens, A. M.; Gierse, J. K.; McDonald, J. J.; Stegeman, R. A.; Pak, J. Y.; Gildehaus, D.; Miyashiro, J. M.; Penning, T. D.; Seibert, K.; Isakson, P. C.; Stallings, W. C. Nature 1996, 384, 644–648. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. 56. Adams, S. S. J. Clin. Pharmacol. 1992, 32, 317–323. The propionic acids: a personal perspective. 57. Trelle, S.; Reichenbach, S.; Wandel, S.; Hildebrand, P.; Tschannen, B.; Villiger, P. M.; Egger, M.; Juni, P. BMJ 2011, 342, c7086. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. 58. Gupta, G. P.; Nguyen, D. X.; Chiang, A. C.; Bos, P. D.; Kim, J. Y.; Nadal, C.; 122 Gomis, R. R.; Manova-Todorova, K.; Massague, J. Nature 2007, 446, 765–770. Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. 59. (a) Morphy, R.; Kay, C.; Rankovic, Z. Drug Discov. Today 2004, 9, 641–651. From magic bullets to designed multiple ligands; (b) Morphy, R.; Rankovic, Z. J. Med. Chem. 2006, 49, 4961–4970. The physicochemical challenges of designing multiple ligands. 60. Lolli, M. L.; Cena, C.; Medana, C.; Lazzarato, L.; Morini, G.; Coruzzi, G.; Manarini, S.; Fruttero, R.; Gasco, A. J. Med. Chem. 2001, 44, 3463–3468. A new class of ibuprofen derivatives with reduced gastrotoxicity. 61. Buijsman, R. C.; Basten, J. E.; van Dinther, T. G.; van der Marel, G. A.; van Boeckel, C. A.; van Boom, J. H. Bioorg. Med. Chem. Lett. 1999, 9, 2013–2018. Design and synthesis of a novel synthetic NAPAP-penta-saccharide conjugate displaying a dual antithrombotic action. 62. Murugesan, N.; Tellew, J. E.; Gu, Z.; Kunst, B. L.; Fadnis, L.; Cornelius, L. A.; Baska, R. A.; Yang, Y.; Beyer, S. M.; Monshizadegan, H.; Dickinson, K. E.; 123 Panchal, B.; Valentine, M. T.; Chong, S.; Morrison, R. A.; Carlson, K. E.; Powell, J. R.; Moreland, S.; Barrish, J. C.; Kowala, M. C.; Macor, J. E. J. Med. Chem. 2002, 45, 3829–3835. Discovery of N-isoxazolyl biphenylsulfonamides as potent dual angiotensin II and endothelin A receptor antagonists. 63. Barbey, S.; Goossens, L.; Taverne, T.; Cornet, J.; Choesmel, V.; Rouaud, C.; Gimeno, G.; Yannic-Arnoult, S.; Michaux, C.; Charlier, C.; Houssin, R.; Henichart, J. P. Bioorg. Med. Chem. Lett. 2002, 12, 779–782. Synthesis and activity of a new methoxytetrahydropyran derivative as dual cyclooxygenase-2/5-lipoxygenase inhibitor. 64. Govorkova, E. A.; Webster, R. G. Viruses 2010, 2, 1510–1529. Combination chemotherapy for influenza. 65. Lee, S. M.; Cheung, C. Y.; Nicholls, J. M.; Hui, K. P.; Leung, C. Y.; Uiprasertkul, M.; Tipoe, G. L.; Lau, Y. L.; Poon, L. L.; Ip, N. Y.; Guan, Y.; Peiris, J. S. J. Infect. Dis. 2008, 198, 525–535. Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza 124 H5N1 infection. 66. Salomon, R.; Hoffmann, E.; Webster, R. G. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 12479–12481. Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. 67. Ottolini, M.; Blanco, J.; Porter, D.; Peterson, L.; Curtis, S.; Prince, G. Pediatr. Pulmonol. 2003, 36, 290–294. Combination anti-inflammatory and antiviral therapy of influenza in a cotton rat model. 68. Shie, J.-J.; Fang, J.-M.; Wang, S.-Y.; Tsai, K.-C.; Cheng, Y.-S. E.; Yang, A.-S.; Hsiao, S.-C.; Su, C.-Y.; Wong, C.-H. J. Am. Chem. Soc. 2007, 129, 11892–11893. Synthesis of Tamiflu and its Phosphonate Congeners Possessing Potent Anti-Influenza Activity. 69. Shie, J.-J.; Fang, J.-M.; Lai, P.-T.; Wen, W.-H.; Wang, S.-Y.; Cheng, Y.-S. E.; Tsai, K.-C.; Yang, A.-S.; Wong, C.-H. J. Am. Chem. Soc. 2011, 133, 17959–17965. A practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity. 125 70. Chandler, M.; Bamford, M. J.; Conroy, R.; Lamont, B.; Patel, B.; Patel, V. K.; Steeples, I. P.; Storer, R.; Weir, N. G.; Wright, M.; Williamson, C. J. Chem. Soc. Perkin Trans. 1 1995, 1173–1180. Synthesis of the potent influenza neuraminidase inhibitor 4-guanidino Neu5Ac2en. X-Ray molecular structure of 5-acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-D-erythro-L-gluco-nononic acid. 71. Chang, C.-W.; Norsikian, S.; Guillot, R.; Beau, J.-M. Eur. J. Org. Chem. 2010, 2280–2294. Regio- and stereocontrolled palladium-catalyzed allylic substitution on N-acetylneuraminic acid derivatives. 72. Zheng, B. J.; Chan, K. W.; Lin, Y. P.; Zhao, G. Y.; Chan, C.; Zhang, H. J.; Chen, H. L.; Wong, S. S.; Lau, S. K.; Woo, P. C.; Chan, K. H.; Jin, D. Y.; Yuen, K. Y. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 8091–8096. Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus. 73. Liu, K.-C.; Fang, J.-M.; Jan, J.-T.; Cheng, T.-J. R.; Wang, S.-Y.; Yang, S.-T.; Cheng, Y.-S. E.; Wong, C.-H. J. Med. Chem. 2012, 55, 8493–8501. Enhanced 126 anti-influenza agents conjugated with anti-inflammatory activity. 74. Lejal, N.; Tarus, B.; Bouguyon, E.; Chenavas, S.; Bertho, N.; Delmas, B.; Ruigrok, R. W. H.; Primo, C. D.; Slama-Schwok, A. Antimicrob. Agents Chemother. 2013, 57, 2231–2242. Structure-based discovery of the novel antiviral properties of naproxen against the nucleoprotein of influenza A virus. 75. Russell, R. J.; Haire, L. F.; Stevens, D. J.; Collins, P. J.; Lin, Y. P.; Blackburn, G. M.; Hay, A. J.; Gamblin, S. J.; Skehel, J. J. Nature 2006, 443, 45–49. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. 76. Wen, W. H.; Wang, S. Y.; Tsai, K. C.; Cheng, Y. S.; Yang, A. S.; Fang, J. M.; Wong, C. H. Bioorg. Med. Chem. 2010, 18, 4074–4084. Analogs of zanamivir with modified C4-substituents as the inhibitors against the group-1 neuraminidases of influenza viruses. 77. Udommaneethanakit, T. R., T.; Bren, U.; Frecer, V.; Stanislav, M. J. Chem. Inf. Model. 2009, 49, 2323–2332. Dynamic behavior of avian influenza A virus 127 neuraminidase subtype H5N1 in complex with oseltamivir, zanamivir, peramivir, and their phosphonate analogues. 78. Fukuyama, T. J., C.-K.; Cheung, M. Tetrahedron Lett. 1995, 36, 6373–6374. 2- and 4-nitrobenzenesulfonamides: exceptionally versatile means for preparation of secondary amines and protection of amines. 79. Bross, I. Biometrics 6, 413–423. Estimates of the LD50: A critique. 80. Kerrigan, F. M., C.; Thomas, G. H. Tetrahedron Lett. 1998, 39, 2219–2222. Synthesis of arylpiperazines via palladium-catalysed aromatic amination reactions of bromoarenes with N-tert-butoxycarbonylpiperazine. 128 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59067 | - |
| dc.description.abstract | 流行性感冒（influenza）為一種急性呼吸道疾病，由流感病毒所引起，發病快速，在歷史上爆發過的全球性疫情不勝枚舉，特別是近幾年來的H5N1 的禽流感以及H1N1的新型流感最為嚴重。瑞樂沙及克流感為治療流感最主要的兩種藥物，以病毒的神經胺酸酶作為抑制目標。神經胺酸酶在病毒的生命週期扮演很重要的角色，從演化的角度來看，不同亞型的神經胺酸酶可依照其相似程度分成兩大群：包含N1、N4、N5、N8 的group-1 以及包含N2、N3、N6、N7、N9 的 group-2，group-1 的神經胺酸酶在構型上多出了一個可結合空間，稱為150-cavity。因此我們以150-cavity 為目標，設計新型抗流感藥物。另一方面，當病人感染流感時，病毒所引發的嚴重發炎反應會產生許多嚴重併發症如肺炎，提高了病患的致死率。因此，我們設計出新型雙標靶（dual-target）藥物，結合抗流感藥物以及抗發炎藥物，希望在治療流感藥物上能有更好的成效。
之前本實驗室已經開發出瑞樂沙磷衍生物的合成方法，我們在此進一步合成中間體26，並針對不同目標來做化學結構上的修飾。我們已經成功合成出化成物34以及化合物39，期望此類新型雙標靶藥物能夠抑制發炎反應並同時具有抗病毒療效，目前生物活性測試正在進行中。 另一方面，以group-1的神經胺酸脢為抑制目標的化合物42和43目前還在和成階段，未來希望對於疫情嚴重的H5N1能夠有很有的抑制效果。 | zh_TW |
| dc.description.abstract | Influenza is a severe viral infection of respiratory system. The outbreaks of worldwide H5N1 avian influenza and the new type pandemic H1N1 human flu have heightened the
threat of public health. Zanamivir and oseltamivir are the main anti-influenza drugs targeting the neuraminidase (NA) of influenza virus. NA plays an important role in the life cycle of influenza viruses. There are two phylogenetically distinct groups of NAs of influenza A viruses: group-1 NAs include the N1, N4, N5, and N8 subtypes, and group-2 NAs include the N2, N3, N6, N7, and N9 subtypes. The group-1 NA contains a flexible loop and a cavity, so-called “150-cavity” near the binding pocket S2. Based on this rationale, we designed new inhibitors, which targeted 150-cavity of group-1 NA for better inhibitory activity. On the other hand, the uncontrolled virus-induced cytokines could cause the high mortality of human infected by H5N1 avian influenza virus. We explored the novel dual-target bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents. Our research group has developed the zanamivir phosphonate congeners, which have better inhibitory activities. In this study I synthesized the pivotal intermediate compound 26, and further modified the C4-substituent for two specific aims. We successfully synthesized compounds 34 and 39 by conjugating the phosphono-zanamivir with anti-inflammatory agents as new dual-target drugs against influenza viruses. The bioactivity of compounds 34 and 39 is currently under investigation. We also designed the phosphono-zanamivir derivatives 42 and 43 having additional bindings to the 150-cavity of group-1 NAs. The synthetic work is in progress. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T08:47:57Z (GMT). No. of bitstreams: 1 ntu-102-R00223159-1.pdf: 15441807 bytes, checksum: b208faf514d3df54290a8f9d3577fc57 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 中文摘要 ......................................................................................................................... I
Abstract ......................................................................................................................... III 目錄 ............................................................................................................................... V 表目錄 ....................................................................................................................... VIII 圖目錄 .......................................................................................................................... IX 流程目錄 .................................................................................................................... XII 簡稱用語對照表 ....................................................................................................... XIII 第一章 緒論 .................................................................................................................. 1 第一節 流行性感冒病毒與人類 .......................................................................... 1 第二節 流感病毒簡介 .......................................................................................... 3 2－1 流感病毒種類及介紹 .......................................................................... 3 2－2 流感病毒的生命週期 .......................................................................... 5 2－3 流感病毒表面兩個重要的膜蛋白 ...................................................... 8 2－3－1 血球凝集素（Hemagglutinin，HA） .................................. 8 2－3－2 神經胺酸酶（Neuraminidase，NA） ................................ 10 2－4 離子通道蛋白（M2 ion-channel） ................................................. 12 第三節 流感藥物的開發 .................................................................................... 13 3－1 M2 離子通道抑制劑（M2 ion channel inhibitor） ........................ 13 VI 3－2 血球凝集素抑制劑（hemagglutinin inhibitor） ............................ 15 3－3 神經胺酸酶抑制劑（neuraminidase inhibitor） ............................ 16 3－3－1 Zanamivir 的開發 .............................................................. 18 3－3－2 Zanamivir 的修飾以及改進 .............................................. 20 3－3－3 Oseltamivir 的開發 ........................................................... 23 3－3－3 Peramivir 的開發 .............................................................. 26 3－3－4 流感病毒的抗藥性 ............................................................ 28 3－3－5 零流感（Tamiphosphor）的發展 ..................................... 32 第四節 發炎反應與藥物 .................................................................................... 34 4－1 抗發炎藥物的開發 .......................................................................... 35 4－2 Naproxen 和Ibuprofen ..................................................................... 38 第五節 多標靶治療（Multi-target therapy） .................................................... 39 第六節 抗流感以及抗發炎合併治療 ................................................................ 42 第二章 結果與討論 .................................................................................................... 44 第一節 研究背景與目的 .................................................................................... 44 第二節 Phosphono-zanamivir 衍生物的合成 .................................................... 47 第三節 設計雙標靶抗流感藥物 ........................................................................ 50 3－1 設計概念 .......................................................................................... 50 3－2 雙標靶藥物的合成 .......................................................................... 52 3－2－1 Ibuprofen 衍生物的合成 ................................................... 52 VII 3－2－2 Naproxen 衍生物的合成 ................................................... 56 3－3 離體培養活性測試 .......................................................................... 57 3－3－1 活性測試方法 .................................................................... 57 3－3－2 抗流感活性測試結果與討論 ............................................ 59 3－4 結論 .................................................................................................. 61 第四節 針對流感病毒上N1 開放式構型選擇性合成神經胺酸酶抑制劑 ..... 62 4－1 設計概念 .......................................................................................... 62 4－2 化合物44、45 的合成 .................................................................... 67 4－3 結論 .................................................................................................. 73 第五節 總結 ........................................................................................................ 74 第三章 實驗部分 ........................................................................................................ 77 第一節 General Part ............................................................................................ 77 第二節 Procedures of Bioassay ........................................................................... 79 第三節 Synthestic Procedures and Characterization of Compounds .................. 82 第四章 參考文獻 ...................................................................................................... 107 附錄 化合物之核磁共振光譜 ................................................................................ 129 | |
| dc.language.iso | zh-TW | |
| dc.title | 合成瑞樂沙磷衍生物來對抗流感病毒 | zh_TW |
| dc.title | Design and synthesis of phosphono-zanamivir derivatives against influenza virus | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 羅禮強,李文山,簡敦誠 | |
| dc.subject.keyword | 流感病毒,瑞樂沙, | zh_TW |
| dc.subject.keyword | influenza virus,zanamivir, | en |
| dc.relation.page | 179 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-20 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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