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Synthesis 2006(4): 711-715  
DOI: 10.1055/s-2006-926308
PAPER
© Georg Thieme Verlag Stuttgart · New York

Expedited Synthesis of Substituted Dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones Structurally Related to Granulatimide

Hélène Hénona, Fabrice Anizona, Nathalie Kucharczykb, Armelle Loynelb, Patrick Casarab, Bruno Pfeifferb, Michelle Prudhomme*a
a Laboratoire SEESIB, Université Blaise Pascal, UMR 6504 du CNRS, 63177 Aubière, France
b Institut de Recherches SERVIER, Division Recherche Cancérologie, 125 Chemin de ronde, 78290 Croissy sur Seine, France
Fax: +33(4)73407717; e-Mail: Michelle.PRUDHOMME@univ-bpclermont.fr;
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Publication History

Received 14 July 2005
Publication Date:
19 January 2006 (online)

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Abstract

Dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones can be considered as granulatimide analogues. In view of structure-activity relationship studies in these series, a parallel liquid-phase microwave-assisted synthesis was developed to generate a small library of compounds bearing various substituents at positions 8, 9, 10, or 11 on the aromatic framework.

Key words

parallel synthesis - granulatimide - antitumor agents - dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraone

    References

  • 1 Berlinck RGS. Britton R. Piers E. Lim L. Roberge M. Moreira da Rocha R. Andersen RJ. J. Org. Chem.  1998,  63:  9850 
    CrossrefGoogle Scholar
  • 2 Roberge M. Berlinck RGS. Xu L. Andersen HJ. Lim LY. Curman D. Stringer CM. Friend SH. Davies P. Vincent I. Haggarty SJ. Kelly MT. Britton R. Piers E. Anderson RJ. Cancer Res.  1998,  58:  5701 
    Google Scholar
  • 3 Andersen RJ, Roberge M, Sanghera J, and Leung D. inventors; International Patent  WO99/47522.  ; Chem. Abstr. 1999, 131, 243451
  • 4 Jiang X. Zhao B. Britton R. Lim LY. Leong D. Sanghera JS. Zhou BB. Piers E. Andersen RJ. Roberge M. Mol. Cancer Ther.  2004,  3:  1221 
    Google Scholar
  • 5 Kawabe T. Mol. Cancer Ther.  2004,  3:  513 
    Google Scholar
  • 6 Prudhomme M. Curr. Med. Chem: Anti-Cancer Agents  2004,  4:  435 
    Google Scholar
  • 7 Zhou BB. Bartek J. Nat. Rev. Cancer  2004,  4:  216 
    CrossrefGoogle Scholar
  • 8 Dancey J. Sausville EA. Nat. Rev. Drug Discovery  2003,  2:  296 
    CrossrefGoogle Scholar
  • 9 Senderowicz AM. Cancer Biol. Ther.  2003,  2:  S84 
    Google Scholar
  • 10 Sausville EA. Elsayed Y. Monga M. Kim G. Annu. Rev. Pharmacol. Toxicol.  2003,  43:  199 
    CrossrefGoogle Scholar
  • 11 Piers E. Britton R. Andersen RJ. J. Org. Chem.  2000,  65:  530 
    CrossrefGoogle Scholar
  • 12 Yoshida T. Nishiyachi M. Nakashima N. Murase M. Kotani E. Chem. Pharm. Bull.  2002,  50:  872 
    CrossrefGoogle Scholar
  • 13 Terpin A. Winklhofer C. Schumann S. Steglich W. Tetrahedron  1998,  54:  1745 
    CrossrefGoogle Scholar
  • 14 Hugon B. Pfeiffer B. Renard P. Prudhomme M. Tetrahedron Lett.  2003,  44:  3927 
    CrossrefGoogle Scholar
  • 15 Hugon B. Pfeiffer B. Renard P. Prudhomme M. Tetrahedron Lett.  2003,  44:  4607 
    CrossrefGoogle Scholar
  • 16 Hugon B. Pfeiffer B. Renard P. Prudhomme M. Tetrahedron Lett.  2003,  44 3935 
    Google Scholar
  • 17 Ator MA, Bihovsky R, Chatterjee S, Dunn D, and Hudkins RL. inventors; International Patent  WO01/85686 A2.  ; Chem. Abstr. 2001, 135, 371989
  • 18 Hénon H. Messaoudi S. Hugon B. Anizon F. Pfeiffer B. Prudhomme M. Tetrahedron  2005,  61:  5599 
    CrossrefGoogle Scholar
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For SPE purifications, Waters Oasis HLB extraction cartridges (6 g) were used with the following eluents: H2O, then H2O-MeCN (80:20), and then MeCN. For some compounds a gradient performed with Jones Flash master II was necessary. After evaporation, Et2O was added to the solid residues, the compounds were filtered and dried.