Dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including H5N1 avian influenza

Journal of Medicinal Chemistry

Volumn 48, Issue 8, 2005, Pages 2964-2971

  Macdonald, Simon J F ^a   Cameron, Rachel ^b   Demaine, Derek A ^a   Fenton, Rob J ^a   Foster, Graham ^a   Gower, David ^a   Hamblin, J Nicole ^a   Hamilton, Stephanie ^b   Hart, Graham J ^a   Hill, Alan P ^a   Inglis, Graham G A ^a   Jin, Betty ^b   Jones, Haydn T ^a   McConnell, Darryl B ^b   McKimm Breschkin, Jennifer ^c   Mills, Gail ^a   Nguyen, Van ^b   Owens, Ian J ^a   Parry, Nigel ^a   Shanahan, Stephen E ^a   Smith, Donna ^a   Watson, Keith G ^b,d   Wu, Wen Yang ^b   Tucker, Simon P ^b   more..

^a GLAXOSMITHKLINE   (United Kingdom)

^b Biota Holdings Limited   (Australia)

^c CSIRO   (Australia)

^d WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; SIALIDASE; SIALIDASE INHIBITOR; UNCLASSIFIED DRUG; ZANAMIVIR; ZANAMIVIR DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIVIRAL ACTIVITY; ARTICLE; AVIAN INFLUENZA; CONTROLLED STUDY; DIMERIZATION; DRUG CLEARANCE; DRUG CONJUGATION; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG POTENCY; DRUG TISSUE LEVEL; ENZYME INHIBITION; INFECTION PREVENTION; INFLUENZA; INFLUENZA VIRUS A; INFLUENZA VIRUS B; LUNG PARENCHYMA; MALE; NONHUMAN; RAT; VIRUS INHIBITION; VIRUS STRAIN;

ANIMALS; ANTIVIRAL AGENTS; CELL LINE; CRYSTALLIZATION; DIMERIZATION; GUANIDINES; INFLUENZA A VIRUS; INFLUENZA A VIRUS, H5N1 SUBTYPE; INFLUENZA B VIRUS; LUNG; MALE; MEMBRANES, ARTIFICIAL; MICE; MODELS, MOLECULAR; MOLECULAR WEIGHT; NEURAMINIDASE; ORTHOMYXOVIRIDAE INFECTIONS; PLAQUE ASSAY; PYRANS; RATS; RATS, SPRAGUE-DAWLEY; SIALIC ACIDS; STEREOISOMERISM; ZANAMIVIR;

EID: 20944450978     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040891b     Document Type: Article

References (28)

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5. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R.; Rational Design of Potent Sialidase-Based Inhibitors of Influenza Virus Replication. Nature 1993, 363, 418-423. For recent reviews on neuraminidase inhibitors, see: Klumpp, K. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2004, 14, 1153-1168; Wang, G. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2002, 12, 845-861. Abdel-Magid, A. F.; Maryanoff, C. A.; Mehrman, S. J. Synthesis of Influenza Neuraminidase Inhibitors. Curr. Opin. Drug Discuss. Dev. 2001, 4, 776-791. For leading references on other neuraminidase inhibitors, see: Abbott Laboratories: Wang, G. T.; Chen, Y.; Wang, S.; Gentles, R.; Sowin, T.; Kati, W.; Muchmore, S.; Giranda, V.; Stewart, K.; Sham, H.; Kempf, D.; Laver, W. G. Design, Synthesis, and Structural Analysis of Influenza Neuraminidase Inhibitors Containing Pyrrolidine Cores. J. Med. Chem. 2001, 44, 1192-1201. BioCryst: Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. S. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a Novel, Highly Potent, Orally Active, and Selective Influenza Neuraminidase Inhibitor through Structure-based Drug Design. J. Med. Chem. 2000, 43, 3482-3486; Chand, P.; Babu, Y. S.; Bantia, S.; Rowland, S.; Dehghani, A.; Kotian, P. L.; Hutchison, T. L.; Ali, S.; Brouillette, W.; El-Kattan, Y.; Lin, T.-H. Syntheses and Neuraminidase Inhibitory Activity of Multisubstituted Cyclopentane Amide Derivatives. J. Med. Chem. 2004, 47, 1919-1929. Sankyo: Honda, T.; Yoshida, S.; Arai, M.; Masuda, T.; Yamashita, M. Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors bearing 4-Guanidino-Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1929-1932; Honda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and Anti-Influenza Virus Activity of 7-O-Alkylated Derivatives Related to Zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925-1928.
6. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R.; Rational Design of Potent Sialidase-Based Inhibitors of Influenza Virus Replication. Nature 1993, 363, 418-423. For recent reviews on neuraminidase inhibitors, see: Klumpp, K. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2004, 14, 1153-1168; Wang, G. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2002, 12, 845-861. Abdel-Magid, A. F.; Maryanoff, C. A.; Mehrman, S. J. Synthesis of Influenza Neuraminidase Inhibitors. Curr. Opin. Drug Discuss. Dev. 2001, 4, 776-791. For leading references on other neuraminidase inhibitors, see: Abbott Laboratories: Wang, G. T.; Chen, Y.; Wang, S.; Gentles, R.; Sowin, T.; Kati, W.; Muchmore, S.; Giranda, V.; Stewart, K.; Sham, H.; Kempf, D.; Laver, W. G. Design, Synthesis, and Structural Analysis of Influenza Neuraminidase Inhibitors Containing Pyrrolidine Cores. J. Med. Chem. 2001, 44, 1192-1201. BioCryst: Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. S. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a Novel, Highly Potent, Orally Active, and Selective Influenza Neuraminidase Inhibitor through Structure-based Drug Design. J. Med. Chem. 2000, 43, 3482-3486; Chand, P.; Babu, Y. S.; Bantia, S.; Rowland, S.; Dehghani, A.; Kotian, P. L.; Hutchison, T. L.; Ali, S.; Brouillette, W.; El-Kattan, Y.; Lin, T.-H. Syntheses and Neuraminidase Inhibitory Activity of Multisubstituted Cyclopentane Amide Derivatives. J. Med. Chem. 2004, 47, 1919-1929. Sankyo: Honda, T.; Yoshida, S.; Arai, M.; Masuda, T.; Yamashita, M. Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors bearing 4-Guanidino-Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1929-1932; Honda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and Anti-Influenza Virus Activity of 7-O-Alkylated Derivatives Related to Zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925-1928.
7. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R.; Rational Design of Potent Sialidase-Based Inhibitors of Influenza Virus Replication. Nature 1993, 363, 418-423. For recent reviews on neuraminidase inhibitors, see: Klumpp, K. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2004, 14, 1153-1168; Wang, G. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2002, 12, 845-861. Abdel-Magid, A. F.; Maryanoff, C. A.; Mehrman, S. J. Synthesis of Influenza Neuraminidase Inhibitors. Curr. Opin. Drug Discuss. Dev. 2001, 4, 776-791. For leading references on other neuraminidase inhibitors, see: Abbott Laboratories: Wang, G. T.; Chen, Y.; Wang, S.; Gentles, R.; Sowin, T.; Kati, W.; Muchmore, S.; Giranda, V.; Stewart, K.; Sham, H.; Kempf, D.; Laver, W. G. Design, Synthesis, and Structural Analysis of Influenza Neuraminidase Inhibitors Containing Pyrrolidine Cores. J. Med. Chem. 2001, 44, 1192-1201. BioCryst: Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. S. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a Novel, Highly Potent, Orally Active, and Selective Influenza Neuraminidase Inhibitor through Structure-based Drug Design. J. Med. Chem. 2000, 43, 3482-3486; Chand, P.; Babu, Y. S.; Bantia, S.; Rowland, S.; Dehghani, A.; Kotian, P. L.; Hutchison, T. L.; Ali, S.; Brouillette, W.; El-Kattan, Y.; Lin, T.-H. Syntheses and Neuraminidase Inhibitory Activity of Multisubstituted Cyclopentane Amide Derivatives. J. Med. Chem. 2004, 47, 1919-1929. Sankyo: Honda, T.; Yoshida, S.; Arai, M.; Masuda, T.; Yamashita, M. Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors bearing 4-Guanidino-Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1929-1932; Honda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and Anti-Influenza Virus Activity of 7-O-Alkylated Derivatives Related to Zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925-1928.
8. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R.; Rational Design of Potent Sialidase-Based Inhibitors of Influenza Virus Replication. Nature 1993, 363, 418-423. For recent reviews on neuraminidase inhibitors, see: Klumpp, K. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2004, 14, 1153-1168; Wang, G. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2002, 12, 845-861. Abdel-Magid, A. F.; Maryanoff, C. A.; Mehrman, S. J. Synthesis of Influenza Neuraminidase Inhibitors. Curr. Opin. Drug Discuss. Dev. 2001, 4, 776-791. For leading references on other neuraminidase inhibitors, see: Abbott Laboratories: Wang, G. T.; Chen, Y.; Wang, S.; Gentles, R.; Sowin, T.; Kati, W.; Muchmore, S.; Giranda, V.; Stewart, K.; Sham, H.; Kempf, D.; Laver, W. G. Design, Synthesis, and Structural Analysis of Influenza Neuraminidase Inhibitors Containing Pyrrolidine Cores. J. Med. Chem. 2001, 44, 1192-1201. BioCryst: Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. S. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a Novel, Highly Potent, Orally Active, and Selective Influenza Neuraminidase Inhibitor through Structure-based Drug Design. J. Med. Chem. 2000, 43, 3482-3486; Chand, P.; Babu, Y. S.; Bantia, S.; Rowland, S.; Dehghani, A.; Kotian, P. L.; Hutchison, T. L.; Ali, S.; Brouillette, W.; El-Kattan, Y.; Lin, T.-H. Syntheses and Neuraminidase Inhibitory Activity of Multisubstituted Cyclopentane Amide Derivatives. J. Med. Chem. 2004, 47, 1919-1929. Sankyo: Honda, T.; Yoshida, S.; Arai, M.; Masuda, T.; Yamashita, M. Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors bearing 4-Guanidino-Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1929-1932; Honda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and Anti-Influenza Virus Activity of 7-O-Alkylated Derivatives Related to Zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925-1928.
9. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R.; Rational Design of Potent Sialidase-Based Inhibitors of Influenza Virus Replication. Nature 1993, 363, 418-423. For recent reviews on neuraminidase inhibitors, see: Klumpp, K. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2004, 14, 1153-1168; Wang, G. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2002, 12, 845-861. Abdel-Magid, A. F.; Maryanoff, C. A.; Mehrman, S. J. Synthesis of Influenza Neuraminidase Inhibitors. Curr. Opin. Drug Discuss. Dev. 2001, 4, 776-791. For leading references on other neuraminidase inhibitors, see: Abbott Laboratories: Wang, G. T.; Chen, Y.; Wang, S.; Gentles, R.; Sowin, T.; Kati, W.; Muchmore, S.; Giranda, V.; Stewart, K.; Sham, H.; Kempf, D.; Laver, W. G. Design, Synthesis, and Structural Analysis of Influenza Neuraminidase Inhibitors Containing Pyrrolidine Cores. J. Med. Chem. 2001, 44, 1192-1201. BioCryst: Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. S. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a Novel, Highly Potent, Orally Active, and Selective Influenza Neuraminidase Inhibitor through Structure-based Drug Design. J. Med. Chem. 2000, 43, 3482-3486; Chand, P.; Babu, Y. S.; Bantia, S.; Rowland, S.; Dehghani, A.; Kotian, P. L.; Hutchison, T. L.; Ali, S.; Brouillette, W.; El-Kattan, Y.; Lin, T.-H. Syntheses and Neuraminidase Inhibitory Activity of Multisubstituted Cyclopentane Amide Derivatives. J. Med. Chem. 2004, 47, 1919-1929. Sankyo: Honda, T.; Yoshida, S.; Arai, M.; Masuda, T.; Yamashita, M. Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors bearing 4-Guanidino-Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1929-1932; Honda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and Anti-Influenza Virus Activity of 7-O-Alkylated Derivatives Related to Zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925-1928.
10. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R.; Rational Design of Potent Sialidase-Based Inhibitors of Influenza Virus Replication. Nature 1993, 363, 418-423. For recent reviews on neuraminidase inhibitors, see: Klumpp, K. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2004, 14, 1153-1168; Wang, G. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2002, 12, 845-861. Abdel-Magid, A. F.; Maryanoff, C. A.; Mehrman, S. J. Synthesis of Influenza Neuraminidase Inhibitors. Curr. Opin. Drug Discuss. Dev. 2001, 4, 776-791. For leading references on other neuraminidase inhibitors, see: Abbott Laboratories: Wang, G. T.; Chen, Y.; Wang, S.; Gentles, R.; Sowin, T.; Kati, W.; Muchmore, S.; Giranda, V.; Stewart, K.; Sham, H.; Kempf, D.; Laver, W. G. Design, Synthesis, and Structural Analysis of Influenza Neuraminidase Inhibitors Containing Pyrrolidine Cores. J. Med. Chem. 2001, 44, 1192-1201. BioCryst: Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. S. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a Novel, Highly Potent, Orally Active, and Selective Influenza Neuraminidase Inhibitor through Structure-based Drug Design. J. Med. Chem. 2000, 43, 3482-3486; Chand, P.; Babu, Y. S.; Bantia, S.; Rowland, S.; Dehghani, A.; Kotian, P. L.; Hutchison, T. L.; Ali, S.; Brouillette, W.; El-Kattan, Y.; Lin, T.-H. Syntheses and Neuraminidase Inhibitory Activity of Multisubstituted Cyclopentane Amide Derivatives. J. Med. Chem. 2004, 47, 1919-1929. Sankyo: Honda, T.; Yoshida, S.; Arai, M.; Masuda, T.; Yamashita, M. Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors bearing 4-Guanidino-Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1929-1932; Honda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and Anti-Influenza Virus Activity of 7-O-Alkylated Derivatives Related to Zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925-1928.
11. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R.; Rational Design of Potent Sialidase-Based Inhibitors of Influenza Virus Replication. Nature 1993, 363, 418-423. For recent reviews on neuraminidase inhibitors, see: Klumpp, K. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2004, 14, 1153-1168; Wang, G. Recent Advances in the Discovery and Development of Anti-influenza Drugs. Expert Opin. Ther. Pat. 2002, 12, 845-861. Abdel-Magid, A. F.; Maryanoff, C. A.; Mehrman, S. J. Synthesis of Influenza Neuraminidase Inhibitors. Curr. Opin. Drug Discuss. Dev. 2001, 4, 776-791. For leading references on other neuraminidase inhibitors, see: Abbott Laboratories: Wang, G. T.; Chen, Y.; Wang, S.; Gentles, R.; Sowin, T.; Kati, W.; Muchmore, S.; Giranda, V.; Stewart, K.; Sham, H.; Kempf, D.; Laver, W. G. Design, Synthesis, and Structural Analysis of Influenza Neuraminidase Inhibitors Containing Pyrrolidine Cores. J. Med. Chem. 2001, 44, 1192-1201. BioCryst: Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. S. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a Novel, Highly Potent, Orally Active, and Selective Influenza Neuraminidase Inhibitor through Structure-based Drug Design. J. Med. Chem. 2000, 43, 3482-3486; Chand, P.; Babu, Y. S.; Bantia, S.; Rowland, S.; Dehghani, A.; Kotian, P. L.; Hutchison, T. L.; Ali, S.; Brouillette, W.; El-Kattan, Y.; Lin, T.-H. Syntheses and Neuraminidase Inhibitory Activity of Multisubstituted Cyclopentane Amide Derivatives. J. Med. Chem. 2004, 47, 1919-1929. Sankyo: Honda, T.; Yoshida, S.; Arai, M.; Masuda, T.; Yamashita, M. Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors bearing 4-Guanidino-Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1929-1932; Honda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and Anti-Influenza Virus Activity of 7-O-Alkylated Derivatives Related to Zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925-1928.
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