Skip to main content
SpringerLink
Log in

Synthesis, molecular structure, NMR spectroscopic and computational analysis of a selective adenosine A2A antagonist, ZM 241385

  • Published:
Structural Chemistry Aims and scope Submit manuscript

Abstract

Herein, we describe the synthesis of the adenosine A2A antagonist ZM 241385 (9) starting from commercially available 2-furanhydrazide (1) and including a comprehensive structural characterization of all the intermediates and the final product. In addition, extensive NMR analysis, including temperature and concentration-dependent experiments, are reported as well as the first single-crystal structure of the compound ZM 241385 (9) as the trihydrate. Furthermore, an extensive structural comparison of the single-crystal structure with the published protein bound X-ray structures is reported.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Baraldi PG, Cacciari B, Spalluto G, Borioni A, Viziano M, Dioniotti S, Ongini E (1995) Curr Med Chem 2:707

    CAS  Google Scholar 

  2. Müller CE (2000) Drug Future 25:1043

    Article  Google Scholar 

  3. Richardson PJ, Kase H, Jenner PG (1997) Trends Pharmacol Sci 18(9):338

    Article  CAS  Google Scholar 

  4. Caulkett PWR, Jones G, Collis MG, Poucher SM (1991). European Patent EP 459702, 23 May 1991

  5. Jaakola V-P, Griffith MT, Hanson MA, Cherezov V, Chien EYT, Lane JR, IJzerman AP, Stevens RC (2008) Science 322(5905):1211

    Article  CAS  Google Scholar 

  6. Doré AS, Robertson N, Errey JC, Ng I, Hollenstein K, Tehan B, Hurrell E, Bennett K, Congreve M, Magnani F, Tate CG, Weir M, Marshall FH (2011) Structure 19(9):1283

    Article  Google Scholar 

  7. Minetti P, Tinti MO, Carminati P, Castorina M, Di Cesare MA, Di Serio S, Gallo G, Ghirardi O, Giorgi F, Giorgi L, Piersanti G, Bartoccini F, Tarzia G (2005) J Med Chem 48(22):6887

    Article  CAS  Google Scholar 

  8. Federico S, Paoletta S, Cheong SL, Pastorin G, Cacciari B, Stragliotto S, Klotz KN, Siegel J, Gao Z-G, Jacobson KA, Moro S, Spalluto G (2011) J Med Chem 54(3):877

    Article  CAS  Google Scholar 

  9. Srivastava RP, Kumar VV, Bhatia S, Sharma S (1995) Indian J Chem 34B:209

    CAS  Google Scholar 

  10. Dolzhenko AV, Pastorin G, Dolzhenko AV, Chui WK (2009) Tetrahedron Lett 50:2124

    Article  CAS  Google Scholar 

  11. Caulkett PWR, Jones G, McPartlin M, Renshaw ND, Stewart SK, Wright B (1995) J Chem Soc Perkin Trans 1:801

    Article  Google Scholar 

  12. Kessler H (1970) Angew Chem Int Ed 9:219

    Article  CAS  Google Scholar 

  13. Lunazzi L, Macciantelli D, Grossi L (1983) Tetrahedron 39(2):305

    Article  CAS  Google Scholar 

  14. Anderson JE, Griffith DL, Roberts JD (1969) J Am Chem Soc 91:6371

    Article  CAS  Google Scholar 

  15. Zhukov A, Andrews SP, Errey JC, Robertson N, Tehan B, Mason JS, Marshall FH, Weir M, Congreve M (2011) J Med Chem 54(13):4312

    Article  CAS  Google Scholar 

  16. Yuriev E, Kong DCM, Iskander MN (2004) Eur J Med Chem 39(10):835

    Article  CAS  Google Scholar 

  17. Capuano B, Crosby IT, Forsyth CM, McRobb FM, Moudretski VV, Taylor DA, Vom A, Yuriev E (2010) Struct Chem 21(3):613

    Article  CAS  Google Scholar 

  18. Golzarroshan B, Siddegowda MS, Li HQ, Yathirajan HS, Narayana B, Rathore RS (2012) J Mol Struct 1018:107

    Article  CAS  Google Scholar 

  19. Sheldrick G (2008) Acta Crystallogr A 64(1):112

    Article  CAS  Google Scholar 

  20. Farrugia LJ (1997) J Appl Crystallogr 30(5–1):565

    Article  CAS  Google Scholar 

  21. Farrugia LJ (1999) J Appl Crystallogr 32(4):837

    Article  CAS  Google Scholar 

Download references

Acknowledgments

M.J. is a recipient of the Australian Postgraduate Award Industry (APAI). We thank GlaxoSmithKline, GSK R&D China, Singapore for financial support and Dr. Jason Dang (Monash University) for assistance in obtaining NMR and HRMS data. We also thank Associate Professor Martin Scanlon, Dr Jamie Simpson and Dr James Swarbrick from Monash University for insightful discussions on the NMR aspects in this paper.

Author information

Authors and Affiliations

  1. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Manuela Jörg, Mark Agostino, Elizabeth Yuriev, Peter J. Scammells & Ben Capuano

  2. GlaxoSmithKline, GSK R&D China, Singapore Research Centre, 11 Biopolis Way, Helios Bldg #03-01/02, Singapore, 138667, Singapore

    Frankie S. Mak & Neil D. Miller

  3. Bio21 Molecular Science & Biotechnology Institute, The University of Melbourne, 30 Flemington Road, Parkville, VIC, 3010, Australia

    Jonathan M. White

  4. Western Australian Biomedical Research Institute, Curtin Health Innovation Research Institute, School of Biomedical Sciences, Curtin University, GPO Box U1987, Perth, WA, 6845, Australia

    Mark Agostino

Authors
  1. Manuela Jörg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Agostino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth Yuriev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frankie S. Mak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Neil D. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jonathan M. White
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter J. Scammells
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ben Capuano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ben Capuano.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 1102 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jörg, M., Agostino, M., Yuriev, E. et al. Synthesis, molecular structure, NMR spectroscopic and computational analysis of a selective adenosine A2A antagonist, ZM 241385. Struct Chem 24, 1241–1251 (2013). https://doi.org/10.1007/s11224-012-0151-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11224-012-0151-7

Keywords

Search

Navigation