Skip to main content
SpringerLink
Log in

The Development of Non-Carbohydrate-Based Influenza Virus Sialidase Inhibitors

  • Chapter
  • First Online:
Influenza Virus Sialidase - A Drug Discovery Target

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

The chapter summarises the development of influenza virus sialidase inhibitors that are not structurally derived from carbohydrates, for instance sialic acid. The classification of inhibitor structures, such as the approved drugs oseltamivir and peramivir, is made based on the type of scaffold used, from six-membered aromatic systems to five-membered carbocylic scaffolds. For the most important examples, milestones and unexpected results during their development as well as the respective syntheses are discussed. The last two sections describe natural products with influenza sialidase inhibitory activity which might serve as lead structures in the future and, in brief, discuss the increasing number of in silico studies in the field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. von Itzstein M (2007) The war against influenza: discovery and development of sialidase inhibitors. Nat Rev Drug Discov 6:967–974

    Google Scholar 

  2. De Clerq E (2006) Antiviral agents active against influenza A viruses. Nat Rev 5:1015–1025

    Google Scholar 

  3. Meindl P, Bodo G, Palese P, Schulman J, Tuppy H (1974) Inhibition of neuraminidase activity by derivatives of DANA. Virology 58:457–463

    PubMed  CAS  Google Scholar 

  4. Burmeister W, Henrissat B, Bosso C, Cusack S, Ruigrok RWH (1993) Influenza B virus neuraminidase can synthesize its own inhibitor. Structure 1:19–26

    PubMed  CAS  Google Scholar 

  5. von Itzstein M, Wu W-Y, Kok GB, Pegg MS, Dyason JC, Jin B, Phan TV, Smythe ML, White HF, Oliver SW, Colman PM, Varghese JN, Ryan DM, Woods JM, Bethell RC, Hotham VJ, Cameron JM, Penn CR (1993) Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363:418–423

    Google Scholar 

  6. Rich J, Gehle D, von Itzstein M (eds) (2007) Design and synthesis of sialidase inhibitors for influenza virus infections. Elsevier, Amsterdam

    Google Scholar 

  7. Kiefel M, von Itzstein M (2002) Recent advances in the synthesis of sialic acid derivatives and sialylmimetics as biological probes. Chem Rev 102:471–490

    PubMed  CAS  Google Scholar 

  8. Dyason JC, von Itzstein M (2001) Anti-influenza virus drug design: sialidase inhibitors. Aust J Chem 54:663–670

    CAS  Google Scholar 

  9. Streicher H (2002) Approaches to carboyclic sialidase inhibitors. Monatsh Chem Chem Month 133:1263–1278

    CAS  Google Scholar 

  10. Busse H (ed) (2007) Recent developments in the synthesis and application of sialylimetics. Scion Publishing, Bloxham

    Google Scholar 

  11. Liu Y, Zhang J, Xu W (2007) Recent progress in rational drug design of neuraminidase inhibitors. Curr Med Chem 14:2872–2891

    PubMed  CAS  Google Scholar 

  12. Angata T, Varki A (2002) Chemical diversity in the sialic acids. Chem Rev 102:439–469

    PubMed  CAS  Google Scholar 

  13. Russell RJ, Haire LF, Stevens DJ, Collins PJ, Lin YP, Blackburn GM, Hay AJ, Gamblin SJ, Skehel JJ (2006) The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 443:45–49

    PubMed  CAS  Google Scholar 

  14. Williams M, Bischofberger N, Swaminathan S, Kim CU (1995) Synthesis and influenza neuraminidase inhibitory activity of aromatic analogues of sialic acid. Bioorg Med Chem Lett 5:2251–2254

    CAS  Google Scholar 

  15. Jedrzejas M, Singh S, Brouillette WJ, Laver WG, Air GM, Luo M (1995) Structures of aromatic inhibitors of influenza virus neuraminidase. Biochemistry 34:3144–3151

    PubMed  CAS  Google Scholar 

  16. Chand P, Babu YS, Bantia S, Chu N, Cole LB, Kotian PL, Laver WG, Montgomery JA, Pathak VP, Petty SL, Shrout DP, Walsh DA, Walsh GM (1997) Design and synthesis of benzoic acid derivatives as influenza neuraminidase inhibitors using structure-based drug design. J Med Chem 40:4030–4052

    PubMed  CAS  Google Scholar 

  17. Singh SJM, Air GM, Luo M, Laver WG, Brouilette WJ (1995) Structure-based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction. J Med Chem 38:3217–3225

    PubMed  CAS  Google Scholar 

  18. Chand P, Kotian PL, Morris PE, Bantia S, Walsh DA, Babu YS (2005) Synthesis and inhibitory activity of benzoic acid and pyridine derivatives on influenza neuraminidase. Bioorg Med Chem 13:2665–2678

    PubMed  CAS  Google Scholar 

  19. Sudbeck E, Jedrzejas MJ, Singh S, Brouilette WJ, Air GM, Laver WG, Babu YS, Bantia S, Chand P, Chu N, Montgomery JA, Walsh DA, Luo M (1997) Guanidinobenzoic acid inhibitors of influenza virus neuraminidase. J Mol Biol 267:584–594

    PubMed  CAS  Google Scholar 

  20. Howes PD, Cleasby A, Evans DN, Feilden H, Smith PW, Sollis SL, Taylor N, Wonacott AJ (1999) 4-Acetylamino-3-(imidazol-1-yl)-benzoic acids as novel inhibitors of influenza sialidase. Eur J Med Chem 34:225–234

    CAS  Google Scholar 

  21. Brouillette W, Atigadda VR, Luo M, Air GM, Babu YS, Bantia S (1999) Design of benzoic acid inhibitors of influenza neuraminidase containing a cyclic substitution for the N-acetyl grouping. Bioorg Med Chem Lett 9:1901–1906

    PubMed  CAS  Google Scholar 

  22. Finley JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M (1999) Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site. J Mol Biol 293:1107–1119

    PubMed  CAS  Google Scholar 

  23. Brouillette WJ, Bajpai SN, Ali SM, Velu SE, Atigadda VR, Lommer BS, Finley JB, Luo M, Air GM (2003) Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: modifications of essential pyrrolidinone ring substituents. Bioorg Med Chem 11:2739–2749

    PubMed  CAS  Google Scholar 

  24. Atigadda VR, Brouillette W, Duarte F, Ali SM, Babu YS, Bantia S, Chand P, Chu N, Montgomery JA, Walsh DA, Sudbeck EA et al (1999) Potent inhibition of influenza sialidase by a benzoic acid containing a 2-pyrrolidinone substituent. J Med Chem 42:2332–2343

    PubMed  CAS  Google Scholar 

  25. Zhang J, Wang Q, Fang H, Xu W, Liu A, Du G (2008) Design, synthesis, inhibitory activity, and SAR studies of hydrophobic p-aminosalicylic acid derivatives as neuraminidase inhibitors. Bioorg Med Chem 16:3839–3847

    PubMed  CAS  Google Scholar 

  26. Flashner M, Kessler J, Tanenbaum SW (1983) The interaction of substrate-related ketals with bacterial and viral neuraminidases. Arch Biochem Biophys 221:188–196

    PubMed  CAS  Google Scholar 

  27. Taylor NR, Cleasby A, Singh O, Skarzynski T, Wonacott AJ, Smith PW, Sollis SL, Howes PD, Cherry PC, Bethell R et al (1998) Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus types A and B. J Med Chem 41:798–807

    PubMed  CAS  Google Scholar 

  28. Smith PW, Sollis SL, Howes PD, Cherry PC, Starkey ID, Cobley KN, Weston H, Scicinski J, Merritt A, Whittington A et al (1998) Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 1. Discovery, synthesis, biological activity, and structure and activity relationships of 4-guanidino- and 4-amino-4H-pyran-6-carboxamides. J Med Chem 41:787–797

    PubMed  CAS  Google Scholar 

  29. Wyatt PG, Coomber BA, Evans DN, Jack TI, Fulton HE, Wonacott AJ, Colman P, Varghese J (2001) Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides. Bioorg Med Chem Lett 11:669–673

    PubMed  CAS  Google Scholar 

  30. Kerrigan SA, Smith PW, Stoodley RJ (2001) Synthesis of (4R*,5R*)-4-acetylamino-5-diethylcarbamoylcyclohex-1-ene-1-carboxylic acid and (3R*,4R*)-4-acetylamino-3-diethylcarbamoylcyclohex-1-ene-1-carboxylic acid: new inhibitors of influenza virus sialidases. Tetrahedron Lett 42:4709–4712

    CAS  Google Scholar 

  31. Taylor NR, von Itzstein M (1994) Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. J Med Chem 37:616–624

    PubMed  CAS  Google Scholar 

  32. Vorwerk S, Vasella A (1998) Carbocyclische analoga von NANA. Angew Chem Int Ed Engl 37:1732–1734

    CAS  Google Scholar 

  33. Chandler M, Conroy R, Cooper AWJ, Lamont RB, Scicinski JJ, Smart JE, Storer R, Weir NG, Wilson RD, Wyatt PG (1995) Approaches to carbocyclic analogues of the potent neuraminidase Inhibitor 4-guanidino-Neu5Ac2en. X.Ray molecular structure of N-[(1 S,2S,6R)-2-Azido-6-benzyloxymethyl-4-formylcyclohex-3-enyl]acetamide. J Chem Soc Perkin Trans 1:1189–1197

    Google Scholar 

  34. Kim CU, Lew W, Williams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (1997) Structure − activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors. J Am Chem Soc 119:681–690

    PubMed  CAS  Google Scholar 

  35. Kim C, Lew W, Williams MA, Zhang L, Chen X, Escarpe PA, Mendel DB, Laver WG, Stevens RCJ (1998) 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. J Med Chem 41:2451–2460

    PubMed  CAS  Google Scholar 

  36. Williams MA, Lew W, Mendel DB, Tai CY, Escarpe PA, Laver WG, Stevens RC, Kim CU (1997) Structure-activity relationships of carbocyclic influenza neuraminidase inhibitors. Bioorg Med Chem Lett 7:1837–1842

    CAS  Google Scholar 

  37. Lew W, Wu H, Mendel DB, Escarpe PA, Chen X, Laver WG, Graves BJ, Kim CU (1998) A new series of C3-aza carbocyclic influenza neuraminidase inhibitors: synthesis and inhibitory activity. Bioorg Med Chem Lett 8:3321–3324

    PubMed  CAS  Google Scholar 

  38. Lew W, Wu H, Chen X, Graves BJ, Escarpe PA, MacArthur HL, Mendel DB, Kim CU (2000) Carbocyclic influenza neuraminidase inhibitors possessing a C3-cyclic amine side chain: synthesis and inhibitory activity. Bioorg Med Chem Lett 10:1257–1260

    PubMed  CAS  Google Scholar 

  39. Lew W, Williams MA, Mendel DB, Escarpe PA, Kim CU (1997) C3-Thia and C3-carba isosteres of a carbocyclic influenza neuraminidase inhibitor, (3R,4R,5 S)-4-acetamido-5-amino-3-propoxyl-1-cyclohexene-1-carboxylic acid. Bioorg Med Chem Lett 7:1843–1846

    CAS  Google Scholar 

  40. Zhang L, Williams MA, Mendel DB, Escarpe PA, Kim CU (1997) Synthesis and activity of C2-substituted analogs of influenza neuraminidase inhibitor GS 4071. Bioorg Med Chem Lett 7:1847–1850

    CAS  Google Scholar 

  41. Rohloff JC, Kent KM, Postich MJ, Becker MW, Chapman HH, Kelly DE, Lew W, Louie MS, McGee LR, Prisbe EJ et al (1998) Practical total synthesis of the anti-influenza drug GS-4104. J Org Chem 63:4545–4550

    CAS  Google Scholar 

  42. Abrecht S, Harrington P, Iding H, Karpf M, Trussardi R, Wirz B, Zutter U (2004) The synthetic development of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (tamiflu): a challenge for synthesis and process research. Chimia 58:621–629

    CAS  Google Scholar 

  43. Abrecht S, Federspiel MC, Estermann H, Fischer R, Karpf M, Mair H-J, Oberhauser T, Rimmler G, Trussardi R, Zutter U (2007) The synthetic-technical development of oseltamivir phosphate tamiflutm: a race against time. Chimia 61:93–99

    CAS  Google Scholar 

  44. Karpf M, Trussardi R (2009) Effizienter zugang zu oseltamivirphosphat (tamiflu) über das O-trimesylat von shikimisäureethylester. Angew Chem Int Ed Engl 121:5871–5873

    Google Scholar 

  45. Magano J (2009) Synthetic approaches to the neuraminidase inhibitors zanamivir (relenza) and oseltamivir phosphate (tamiflu) for the treatment of influenza. Chem Rev 109:4398–4438

    PubMed  CAS  Google Scholar 

  46. Shibasaki M, Kanai M (2008) Synthetic strategies for oseltamivir phosphate. Eur J Org Chem:1839–1850

    Google Scholar 

  47. Fukuta Y, Mita T, Fukuda N, Kanai M, Shibasaki M (2006) De novo synthesis of tamiflu via a catalytic asymmetric ring-opening of meso-aziridines with TMSN3. J Am Chem Soc 128:6312–6313

    PubMed  CAS  Google Scholar 

  48. Mita T, Fukuda N, Roca FX, Kanai M, Shibasaki M (2007) Second generation catalytic asymmetric synthesis of tamiflu: allylic substitution route. Org Lett 9:259–262

    PubMed  CAS  Google Scholar 

  49. Yamatsugu K, Kamijo S, Suto Y, Kanai M, Shibasaki M (2007) A concise synthesis of Tamiflu: third generation route via the Diels–Alder reaction and the Curtius rearrangement. Tetrahedron Lett 48:1403–1406

    CAS  Google Scholar 

  50. Yeung Y-Y, Hong S, Corey EJ (2006) A short enantioselective pathway for the synthesis of the anti-influenza neuraminidase inhibitor oseltamivir from 1,3-butadiene and acrylic acid. J Am Chem Soc 128:6310–6311

    PubMed  CAS  Google Scholar 

  51. Kipassa N, Okamura H, Kina K, Hamada T, Iwagawa T (2008) Efficient short step synthesis of Corey’s tamiflu intermediate. Org Lett 10:815–816

    PubMed  CAS  Google Scholar 

  52. Bromfield K, Graden H, Hagberg DP, Olsson T, Kann N (2007) An iron carbonyl approach to the influenza neuraminidase inhibitor oseltamivir. Chem Commun: 3183–3185

    Google Scholar 

  53. Satoh N, Akiba T, Yokoshima S, Fukuyama T (2007) A practical synthesis of (−) oseltamivir. Angew Chem Int Ed Engl 46:5734–5736

    PubMed  CAS  Google Scholar 

  54. Satoh N, Akiba T, Yokoshima S, Fukuyama T (2009) A practical synthesis of (−)-oseltamivir. Tetrahedron 65:3239–3245

    CAS  Google Scholar 

  55. Trost BM, Zhang T (2008) A concise synthesis of (−) oseltamivir. Angew Chem 120:3819–3821

    Google Scholar 

  56. Ishikawa H, Suzuki T, Hayashi Y (2009) High-yielding synthesis of the anti-influenza neuramidase inhibitor (−)-oseltamivir by three ln-one-pot-operations. Angew Chem Int Ed Engl 48:1304–1307

    Google Scholar 

  57. Sun H, Lin YJ, Wu YL, Wu YK (2009) A facile access to antiflu agent tamiflu/oseltamivir. Synlett: 2473–2476

    Google Scholar 

  58. Kamimura A, Nakano T (2010) Use of the diels-alder adduct of pyrrole in organic synthesis. Formal racemic synthesis of tamiflu. J Org Chem 75:3133–3136

    PubMed  CAS  Google Scholar 

  59. Zutter U, Iding H, Spurr P, Wirz B (2008) New, efficient synthesis of oseltamivir phosphate (tamiflu) via enzymatic desymmetrization of a meso-1,3-cyclohexanedicarboxylic acid diester. J Org Chem 73:4895–4902

    PubMed  CAS  Google Scholar 

  60. Shie J-J, Fang J-M, Wang S-Y, Tsai K-C, Cheng Y-SE, Yang A-S, Hsiao S-C, Su C-Y, Wong C-H (2007) Synthesis of tamiflu and its phosphonate congeners possessing potent anti-influenza activity. J Am Chem Soc: 11893–11894

    Google Scholar 

  61. Fleet G, Shing TKM, Warr SM (1984) Enantiospecific synthesis of shikimic acid from d-mannose: formation of a chiralcyclohexene by intramolecular olefination of a carbohydrate-derived intermediate. J Chem Soc Perkin Trans 1:905–908

    Google Scholar 

  62. Mirza S, Vasella A (1984) Synthesis of methyl shikimate and of diethyl phosphashikimate from d-ribose. Helv Chim Acta 67:1562–1567

    CAS  Google Scholar 

  63. Busse H, Streicher H (2006) Building a successful structural motif into sialylmimetics-cyclohexenephosphonate monoesters as pseudo-sialosides with promising inhibitory properties. Bioorg Med Chem 14:1047–1057

    PubMed  Google Scholar 

  64. Streicher H, Meisch J, Bohner C (2001) Synthesis of xylo-configured cyclohexenephosphonates, versatile precursors of sialidase inhibtor libraries. Tetrahedron 57:8851–8859

    CAS  Google Scholar 

  65. Streicher H, Bohner C (2002) Synthesis of functionalized cyclohexenephosphonates and their inhibitors activity. Tetrahedron 58:7573–7581

    CAS  Google Scholar 

  66. Streicher H (2004) Synthesis and evaluation as sialidase inhibitors of xylo-configured cyclohexenephosphonates carrying glycerol sidechain mimics. Bioorg Med Chem Lett 14:361–364

    PubMed  CAS  Google Scholar 

  67. Sullivan B, Carrera I, Drouin M, Hudlicky T (2009) Symmetry-based design for the chemoenzymatic synthesis of oseltamivir (tamiflu) from ethyl benzoate13. Angew Chem Int Ed Engl 48:4229–4231

    PubMed  CAS  Google Scholar 

  68. Matveenko M, Willis AC, Banwell MG (2008) A chemoenzymatic synthesis of the anti-influenza agent Tamiflu®. Tetrahedron Lett 49:7018–7020

    CAS  Google Scholar 

  69. Shie J-J, Fang J-M, Wong C-H (2008) A concise and flexible synthesis of the potent anti-influenza agents tamiflu and tamiphosphor13. Angew Chem Int Ed Engl 47:5788–5791

    PubMed  CAS  Google Scholar 

  70. Ma J, Zhao Y, Ng S, Zhang J, Zeng J, Than A, Chen P, Liu X-W (2010) Sugar-based synthesis of tamiflu and its inhibitory effects on cell secretion. Chem Eur J 16:4533–4540

    PubMed  CAS  Google Scholar 

  71. Mandai T, Oshitari T (2009) Efficient asymmetric synthesis of oseltamivir from d-mannitol. Synlett 2009:783–786

    Google Scholar 

  72. Oshitari T, Mandai T (2009) Azide-free synthesis of oseltamivir from l-methionine. Synlett 2009:787–789

    Google Scholar 

  73. Carbain BSRM, Collins PJ, Hitchcock PB, Streicher H (2009) Galactose-conjugates of the oseltamivir pharmacophore – new tools for the characterization of influenza virus neuraminidases. Org. Biomol, Chem, 9

    Google Scholar 

  74. Carbain B, Collins Patrick J, Callum L, Martin Stephen R, Hay Alan J, McCauley J, Streicher H (2009) Efficient synthesis of highly active phospha-isosteres of the influenza neuraminidase inhibitor oseltamivir. ChemMedChem 4:335–337

    PubMed  CAS  Google Scholar 

  75. Carbain B, Hitchcock PB, Streicher H (2010) New aspects of the Hunsdiecker-Barton halodecarboxylation–syntheses of phospha-shikimic acid and derivatives. Tetrahedron Lett 51:2717–2719

    CAS  Google Scholar 

  76. Kimura Y, Yamatsugu K, Kanai M, Echigo N, Kuzuhara T, Shibasaki M (2009) Design and synthesis of immobilized Tamiflu analog on resin for affinity chromatography. Tetrahedron Lett 50:3205–3208

    CAS  Google Scholar 

  77. Chan T-H, Xin Y-C, von Itzstein M (1997) Synthesis of phosphonic acid analogues of sialic acids (Neu5Ac and KDN) as potential sialidase inhibitors. J Org Chem 62:3500–3504

    CAS  Google Scholar 

  78. Wallimann K, Vasella A (1990) Phosphonic acid analogues of the N-Acetyl-2-deoxyneuraminic acids. Helv Chim Acta 73:1359–1372

    CAS  Google Scholar 

  79. Vasella A, Wyler R (1991) Synthesis of a phosphonic acid analogue of DANA. Helv Chim Acta 74:451–463

    CAS  Google Scholar 

  80. Hochgurtel M, Biesinger R, Kroth H, Piecha D, Hofmann MW, Krause S, Schaaf O, Nicolau C, Eliseev AV (2003) Ketones as building blocks for dynamic combinatorial libraries: highly active neuraminidase inhibitors generated via selection pressure of the biological target. J Med Chem 46:356–358

    PubMed  Google Scholar 

  81. Hanessian S, Wang J, Montgomery D, Stoll V, Stewart KD, Kati W, Maring C, Kempf D, Hutchins C, Laver WG (2002) Design, synthesis, and neuraminidase inhibitory activity of GS-4071 analogues that utilize a novel hydrophobic paradigm. Bioorg Med Chem Lett 12:3425–3429

    PubMed  CAS  Google Scholar 

  82. Jeong JW, Kim JK, Woo BY, Song BJ, Ha D-C, No Z (2004) A substrate mimetic approach for influenza neuraminidase inhibitors. Bull Korean Chem Soc 25:1575–1577

    CAS  Google Scholar 

  83. Reuters (2009) FDA authorizes emergency use of intravenous antiviral peramivir for 2009 H1N1 influenza for certain patients, settings. http://www.reuters.com/article/idUS10036+24-Oct-2009+PRN20091024

  84. Yamamoto T, Kumazawa H, Inami K, Teshima T, Shiba T (1992) Syntheses of sialic acid isomers with inhibitory activity against neuraminidase. Tetrahedron Lett 33:5791–5794

    CAS  Google Scholar 

  85. Babu YS, Chand P, Bantia S, Kotian P, Dehghani A, El Kattan Y, Lin T, Hutchison TL, Elliott AJ, Parker CD et al (2000) BCX-1812, a highly potent and selective influenza neuraminidase inhibitor. J Med Chem 43:3482–3486

    PubMed  CAS  Google Scholar 

  86. Chand P, Kotian PL, Dehghani A, El-Kattan Y, Lin T-H, Hutchison TL, Babu YS, Bantia S, Elliott AJ, Montgomery JA (2001) Systematic structure-based design and stereoselective synthesis of novel multisubstituted cyclopentane derivatives with potent antiinfluenza activity. J Med Chem 44:4379–4392

    PubMed  CAS  Google Scholar 

  87. Chand P, Bantia S, Kotian PL, El-Kattan Y, Lin T-H, Babu YS (2005) Comparison of the anti-influenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo. Bioorg Med Chem 13:4071–4077

    PubMed  CAS  Google Scholar 

  88. Mineno T, Miller MJ (2003) Stereoselective total synthesis of racemic BCX-1812 (RWJ-270201) for the development of neuraminidase inhibitors as anti-influenza agents. J Org Chem 68:6591–6596

    PubMed  CAS  Google Scholar 

  89. Chand P, Babu YS, Bantia S, Rowland S, Dehghani A, Kotian PL, Hutchison TL, Ali S, Brouillette W, El-Kattan Y et al (2004) Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives. J Med Chem 47:1919–1929

    PubMed  CAS  Google Scholar 

  90. Cui Y, Jiao Z, Gong J, Yu Q, Zheng X, Quan J, Luo M, Yang Z (2009) Development of new stereodiverse diaminocyclitols as inhibitors of influenza virus neuraminidase. Org Lett 12:4–7

    Google Scholar 

  91. Wang GT, Chen Y, Wang S, Gentles R, Sowin T, Kati W, Muchmore S, Giranda V, Stewart K, Sham H et al (2001) Design, synthesis, and structural analysis of influenza neuraminidase inhibitors containing pyrrolidine cores. J Med Chem 44:1192–1201

    PubMed  CAS  Google Scholar 

  92. Stoll V, Stewart KD, Maring CJ, Muchmore S, Giranda V, Gu Y-GY, Wang G, Chen Y, Sun M, Zhao C et al (2003) Influenza neuraminidase inhibitors: Structure-based design of a novel inhibitor series. Biochemistry 42:718–727

    PubMed  CAS  Google Scholar 

  93. Wang GT, Wang S, Gentles R, Sowin T, Maring CJ, Kempf DJ, Kati WM, Stoll V, Stewart KD, Laver G (2005) Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core. Bioorg Med Chem Lett 15:125–128

    PubMed  CAS  Google Scholar 

  94. Maring CJ, Stoll VS, Zhao C, Sun M, Krueger AC, Stewart KD, Madigan DL, Kati WM, Xu Y, Carrick RJ et al (2005) Structure-based characterization and optimization of novel hydrophobic binding interactions in a series of pyrrolidine influenza neuraminidase inhibitors. J Med Chem 48:3980–3990

    PubMed  CAS  Google Scholar 

  95. Abed Y, Nehmé B, Baz M, Boivin G (2008) Activity of the neuraminidase inhibitor A-315675 against oseltamivir-resistant influenza neuraminidases of N1 and N2 subtypes. Antiviral Res 77:163–166

    PubMed  CAS  Google Scholar 

  96. Zhang JXW, Liu A, Du G (2008) Design, synthesis and preliminary evaluation of new pyrrolidine derivatives as neuraminidase inhibitors. Med Chem 4:204–209

    Google Scholar 

  97. Krueger AC, Xu Y, Kati WM, Kempf DJ, Maring CJ, McDaniel KF, Molla A, Montgomery D, Kohlbrenner WE (2008) Synthesis of potent pyrrolidine influenza neuraminidase inhibitors. Bioorg Med Chem Lett 18:1692–1695

    PubMed  CAS  Google Scholar 

  98. Kati WM, Montgomery D, Maring C, Stoll VS, Giranda V, Chen X, Laver WG, Kohlbrenner W, Norbeck DW (2001) Novel {alpha}- and {beta}-amino acid inhibitors of influenza virus neuraminidase. Antimicrob Agents Chemother 45:2563–2570

    PubMed  CAS  Google Scholar 

  99. DeGoey D, Chen H-J, Flosi WJ, Grampovnik DJ, Yeoung CM, Klein LL, Kempf DJ (2002) Enantioselective synthesis of antiinfluenza compound A-315675. J Org Chem 67:5445–5453

    PubMed  CAS  Google Scholar 

  100. Barnes DM, Bhagavatula L, DeMattei J, Gupta A, Hill DR, Manna S, McLaughlin MA, Nichols P, Premchandran R, Rasmussen MW et al (2003) A highly diastereoselective vinylogous Mannich condensation and 1,4-conjugate addition of (Z)-propenyl cuprate in the synthesis of an influenza neuraminidase inhibitor. Tetrahedron Asymmetry 14:3541–3551

    CAS  Google Scholar 

  101. Hanessian S, Bayrakdarian M, Luo X (2002) Total synthesis of A-315675:  a potent inhibitor of influenza neuraminidase. J Am Chem Soc 124:4716–4721

    PubMed  CAS  Google Scholar 

  102. Ryu YB, Kim JH, Park S-J, Chang JS, Rho M-C, Bae K-H, Park KH, Lee WS (2010) Inhibition of neuraminidase activity by polyphenol compounds isolated from the roots of Glycyrrhiza uralensis. Bioorg Med Chem Lett 20:971–974

    PubMed  CAS  Google Scholar 

  103. Jeong HJ, Ryu YB, Park S-J, Kim JH, Kwon H-J, Kim JH, Park KH, Rho M-C, Lee WS (2009) Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem 17:6816–6823

    PubMed  CAS  Google Scholar 

  104. Ryu YB, Curtis-Long MJ, Lee JW, Ryu HW, Kim JY, Lee WS, Park KH (2009) Structural characteristics of flavanones and flavones from Cudrania tricuspidata for neuraminidase inhibition. Bioorg Med Chem Lett 19:4912–4915

    PubMed  CAS  Google Scholar 

  105. Mercader AG, Pomilio AB (2010) QSAR study of flavonoids and biflavonoids as influenza H1N1 virus neuraminidase inhibitors. Eur J Med Chem 45:1724–1730

    PubMed  CAS  Google Scholar 

  106. Hung H-C, Tseng C-P, Yang J-M, Ju Y-W, Tseng S-N, Chen Y-F, Chao Y-S, Hsieh H-P, Shih S-R, Hsu JTA (2009) Aurintricarboxylic acid inhibits influenza virus neuraminidase. Antiviral Res 81:123–131

    PubMed  CAS  Google Scholar 

  107. Grienke U, Schmidtke M, Kirchmair J, Pfarr K, Wutzler P, Duìrrwald R, Wolber G, Liedl KR, Stuppner H, Rollinger JM (2009) Antiviral potential and molecular insight into neuraminidase inhibiting diarylheptanoids from alpinia katsumadai. J Med Chem 53:778–786

    Google Scholar 

  108. An J, Lee DCW, Law AHY, Yang CLH, Poon LLM, Lau ASY, Jones SJM (2009) A novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase. J Med Chem 52:2667–2672

    PubMed  CAS  Google Scholar 

  109. Shibazaki M, Tanaka K, Nagai K, Watanabe M, Fujita S, Suzuki K, Okada G, Yamamoto T (2004) YM-92447 (spinosulfate A), a neuraminidase inhibitor produced by an unidentified pycnidial fungus. J Antibiot 57:812–815

    PubMed  CAS  Google Scholar 

  110. Collins P, Haire LF, Liu J, Russel RJ, Walker PA, Skehel JJ, Martin SR, Hay AJ, Gamblin SJ (2008) Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants. Nature 453:1258–1262

    PubMed  CAS  Google Scholar 

  111. Amaro RE, Minh DDL, Cheng LS, Lindstrom WM, Olson AJ, Lin J-H, Li WW, McCammon JA (2007) Remarkable loop flexibility in avian influenza n1 and its implications for antiviral drug design. J Am Chem Soc 129:7764–7765

    PubMed  CAS  Google Scholar 

  112. Mitrasinovic P (2009) On the Structure-Based design of novel inhibitors of H5N1 influenza A virus neuraminidase (NA). Biophys Chem 140:35–38

    PubMed  CAS  Google Scholar 

  113. Rungrotmongkol T, Frecer V, De-Eknamkul W, Hannongbua S, Miertus S (2009) Design of oseltamivir analogs inhibiting neuraminidase of avian influenza virus H5N1. Antiviral Res 82:51–58

    PubMed  CAS  Google Scholar 

  114. Park JW, Jo WH (2009) Computational design of novel, high-affinity neuraminidase inhibitors for H5N1 avian influenza virus. Eur J Med Chem 45:536–541

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Prof. Jim Hanson for proofreading the manuscript and helpful advice.

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Sussex, Brighton, BN1 9QG, UK

    Hansjörg Streicher & Mathew Stanley

Authors
  1. Hansjörg Streicher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mathew Stanley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hansjörg Streicher .

Editor information

Editors and Affiliations

  1. Gold Coast Campus, Inst. Glycomics, Griffith University, Parklands Drive, Southport, 4215, Queensland, Australia

    Mark von Itzstein

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Basel AG

About this chapter

Cite this chapter

Streicher, H., Stanley, M. (2012). The Development of Non-Carbohydrate-Based Influenza Virus Sialidase Inhibitors. In: von Itzstein, M. (eds) Influenza Virus Sialidase - A Drug Discovery Target. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-7643-8927-7_6

Download citation

Publish with us

Policies and ethics

Search

Navigation