PDF herunterladen
Synthesis 2003(11): 1649-1652
DOI: 10.1055/s-2003-40874
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Access to 2-Amido-5-aryl-8-methoxy-triazolopyridine and 2-Amido-5-morpholino-8-methoxy-triazolopyridine Derivatives as Potential Inhibitors of the Adenosine Receptor Subtypes

Matthias Nettekoven*, Bernd Püllmann, Sébastien Schmitt
F. Hoffmann-LaRoche Ltd., Pharmaceutical Research Basel, Discovery Chemistry, Lead Generation, 4070 Basel, Switzerland
Fax: +41(61)6886459; e-Mail: matthias.nettekoven@roche.com;
Weitere Informationen

Publikationsverlauf

Received 29 April 2003
Publikationsdatum:
25. Juli 2003 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

Two versatile and complementary synthetic strategies towards 2-amido-5-aryl-8-methoxy-triazolopyridine derivatives and 2-amido-5-morpholino-8-methoxy-triazolopyridine derivatives in five steps are presented. The key step in each synthetic route can be constituted as the formation of the respective triazolopyridine derivative precursors in 78% and 57% yield, respectively, through an intermediately formed 4H-[1,2,4]oxadiazol-5-one. The final Suzuki coupling/amidation allowed the straightforward access to the desired triazolopyridine derivatives which have not been described previously. Notably, these triazolopyridine-scaffold bears three vectors of diversity which offer maximum flexibility in design and combinatorial synthesis of molecules with a potentially useful inhibitory activity towards adenosine receptor subtypes.

Key words

triazolopyridine derivatives - 4H-[1,2,4]oxadiazol-5-one - Suzuki coupling - combinatorial chemistry

    References

  • 1a Dunwiddie TV. Masino SA. Annu. Rev. Neuroscience  2001,  24:  31 
    Suche in Google Scholar
  • 1b Klinger M. Freissmuth M. Nanoff C. Cell. Sign.  2002,  14:  99 
    Suche in Google Scholar
  • 2a Muller CE. Scior T. Pharm. Acta Helv.  1993,  68:  77 
    CrossrefSuche in Google Scholar
  • 2b Johansson B. Georgiev V. Fredholm BB. Neuroscience  1997,  80:  1187 
    CrossrefSuche in Google Scholar
  • 2c Svenningsson P. Le Moine C. Fisone G. Fredholm BB. Prog. Neurobiol.  1999,  59:  355 
    CrossrefSuche in Google Scholar
  • 3a Nettekoven M. Synlett  2001,  1917 
    Crossref
  • 3b Brodbeck B. Püllmann B. Schmitt S. Nettekoven M. Tetrahedron Lett.  2003,  44:  1675 
    CrossrefSuche in Google Scholar
  • 4a Arndt KE, Johnson TC, and Ouse DG. inventors; PCT Int. Appl.  WO0238572A1. 
  • 4b Johnson TC, Ehr RJ, Johnston RD, Kleschick WA, William A, Martin TP, Pobanz MA, van Heertum JC, and Mann RK. inventors; US Patent Appl.  US5858924. 
  • 4c van Heertum JC, Kleschick WA, Arndt KE, Costales MJ, Ehr RJ, Bradley KB, Reifschneider W, Benko ZL, Ash ML, and Jachetta JJ. inventors; PCT Int. Appl.  WO9601826A1. 
  • 5 Trapani G. Franco M. Latrofa A. Ricciardi L. Carotti A. Serra M. Sanna E. Biggio G. Liso G. J. Med. Chem.  1999,  42:  3934 
    CrossrefSuche in Google Scholar
  • 6 General procedure described in analogy by: Harrison JJ. Pellegrini JP. Selwitz CM. J. Org. Chem.  1981,  46:  2169 
    Suche in Google Scholar
  • 7 Muci AR. Buchwald SL. Top. Curr. Chem.  2002,  219:  131 
    Suche in Google Scholar
  • 8 Hartwig JF. Handbook of Organopalladium Chemistry for Organic Synthesis  2002,  1:  1051-1096  
    Suche in Google Scholar
  • 9 Chapman GM. Stanforth SP. Berridge R. Pozo-Gonzales C. Skabara PJ. J. Mat. Chem.  2002,  12:  2292 
    Suche in Google Scholar
  • 10a

    General procedure for the synthesis of 2 employed similar reaction conditions as for the synthesis of 1.

  • 10b For a more detailed description of workflow procedures utilised in the preparation of compound arrays please refer to: Nettekoven M. Thomas AW. Curr. Med. Chem.  2002,  9:  2179 
    Suche in Google Scholar