Download PDF
Synthesis 2009(11): 1897-1903  
DOI: 10.1055/s-0028-1088048
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Complementary Synthetic Approaches to Constitutionally Diverse N-Aminoalkylated Isoindolinones: Application to the Synthesis of Falipamil and 5-HT1A Receptor Ligand Analogues

Magali Loriona,b, Axel Couture*a,b, Eric Deniaua,b, Pierre Grandclaudona,b
a LCOP, Université des Sciences et Technologies de Lille 1, Bâtiment C3(2), 59655 Villeneuve d’Ascq, France
Fax: +33(3)20336309; e-Mail: axel.couture@univ-lille1.fr;
b CNRS, UMR 8009 ‘Chimie Organique et Macromoléculaire’, 59655 Villeneuve d’Ascq, France
Further Information

Publication History

Received 21 January 2009
Publication Date:
14 April 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

Different synthetic approaches for the elaboration of poly and diversely substituted isoindolinones tailed with constitutionally diverse aminoalkylated chains have been developed. The key step is based upon the preliminary assembly of the isoindoli­none template equipped with hydroxyalkyl appendages. Subsequent manipulation of the terminal hydroxy functionality afforded the targeted compounds and the synthetic utility of these approaches has been emphasized by the synthesis of the bradycardic agent falipamil and 5-HT1A receptor ligand analogues.

Key words

carbanions - metalation - lactams - ring closure - ring opening

    References

  • 1a Zhao XZ. Semenova EA. Vu BC. Maddali K. Marchand C. Hughes SH. Pommier Y. Burke TR. J. Med. Chem.  2008,  51:  251 
    Google Scholar
  • 1b Maugeri C. Alisi MA. Apicella C. Cellai L. Dragone P. Fioravanzo E. Florio S. Furlotti G. Mangano G. Ombrato R. Luisi R. Pompei R. Rincicotti V. Russo V. Vitiello M. Cazzolla N. Bioorg. Med. Chem.  2008,  16:  3091 
    Google Scholar
  • 1c Govindachari TR. Ravindranath KR. Viswanathan N. J. Chem. Soc., Perkin Trans. 1  1974,  1215 
    Google Scholar
  • 1d Pendrak I. Barney S. Wittrock R. Lambert DM. Kingsbury WD. J. Org. Chem.  1994,  59:  2623 
    Google Scholar
  • 1e Yeo H. Li Y. Fu L. Zhu J.-L. Gullen EA. Dutschman GE. Lee Y. Chung R. Huang E.-S. Austin DJ. Cheng Y.-C. J. Med. Chem.  2005,  48:  534 
    Google Scholar
  • 2a Taylor EC. Zhou P. Jennings LD. Mao Z. Hu B. Jun J.-G. Tetrahedron Lett.  1997,  38:  521 
    Google Scholar
  • 2b Fuska J. Fuskova A. Proksa B. Zb. Pr. Chemickotechnol Fak, SVST  1979-1981 (pub. 1986),  285 ; Chem. Abstr. 1987, 106, 95582
    Google Scholar
  • 3a Zeldis JB. inventors; PCT Int. Appl. WO 043378,  .  ; Chem. Abstr. 2004, 140, 417925
  • 3b Hardcastle IR. Ahmed SU. Atkins H. Calvert AH. Curtin NJ. Farnie G. Golding BT. Griffin RJ. Guyenne S. Hutton C. Källblad P. Kemp SJ. Kitching MS. Newell DR. Norbedo S. Northen JS. Reid RJ. Saravanan K. Willems HMG. Lunec J. Bioorg. Med. Chem. Lett.  2005,  15:  1515 
    Google Scholar
  • 3c Shinji C. Maeda S. Imai K. Yoshida M. Hashimoto Y. Miyachi H. Bioorg. Med. Chem.  2006,  14:  7625 
    Google Scholar
  • 4a Linden M. Hadler D. Hofmann S. Hum. Psychopharmacol.  1997,  12:  445 
    Google Scholar
  • 4b Zhuang Z.-P. Kung M.-P. Mu M. Kung HF. J. Med. Chem.  1998,  41:  157 
    Google Scholar
  • 4c Norman MH. Minick DJ. Rigdon GC. J. Med. Chem.  1996,  39:  149 
    Google Scholar
  • 5 Lippmann W. inventors; US Patent 4 267 189,  .  ; Chem. Abstr. 1981, 95, 61988
  • 6 Lee HJ. Lim SJ. Oh SJ. Moon DH. Kim DJ. Tae J. Yoo KH. Bioorg. Med. Chem. Lett.  2008,  18:  1628 
    CrossrefGoogle Scholar
  • 7a Hamprecht D. Micheli F. Tedesco G. Checchia A. Donati D. Petrone M. Terreni S. Wood M. Bioorg. Med. Chem. Lett.  2007,  17:  428 
    Google Scholar
  • 7b Cappelli A. Anzini M. Vomero S. Mennuni L. Makovec F. Doucet E. Hamon M. Menziani MC. De Benedetti PG. Giorgi G. Ghelardini C. Collina S. Bioorg. Med. Chem.  2002,  10:  779 
    Google Scholar
  • 8 Shinozuka T. Yamamoto Y. Hasegawa T. Saito K. Naito S. Tetrahedron Lett.  2008,  49:  1619 
    CrossrefGoogle Scholar
  • 9 Reiffen M. Eberlein W. Mueller P. Psiorz M. Noll K. Heider J. Lillie C. Kobinger W. Luger P. J. Med. Chem.  1990,  33:  1496 
    CrossrefGoogle Scholar
  • 10a Dai-Ho G. Mariano PS. J. Org. Chem.  1987,  52:  704 
    Google Scholar
  • 10b Lorion M. Couture A. Deniau E. Grandclaudon P. Synthesis  2008,  2141 
    Google Scholar
  • 11 Sarabu R. Cooper JP. Cook CM. Cook CM. Gillespie P. Perrotta AV. Olson GL. Drug Des. Discov.  1998,  15:  191 
    Google Scholar
  • 12 Lillie C. Kobinger W. J. Cardiovasc. Pharmacol.  1983,  5:  1048 
    CrossrefGoogle Scholar
  • 13a Brachmann J. Senges J. Hammann HD. Anders G. Beck L. Braun W. Kubler W. Z. Kardiol.  1979,  68:  635 
    Google Scholar
  • 13b Daemmgen JW. Kadatz R. Diederen W. Arzneim.-Forsch. (Drug Res.)  1981,  31:  666 
    Google Scholar
  • 14a Gross GJ. Daemmgen JW. J. Cardiovasc. Pharmacol.  1987,  10:  123 
    Google Scholar
  • 14b Diederen W. van Meel JCA. J. Mol. Cell. Cardiol.  1986,  18 (Suppl. 2):  16 
    Google Scholar
  • 14c Trach V. Daemmgen JW. J. Mol. Cell. Cardiol.  1986,  18 (Suppl. 2):  20 
    Google Scholar
  • 14d Gross GJ. Daemmgen JW. J. Pharmacol. Exp. Ther.  1986,  238:  422 
    Google Scholar
  • 14e Wenger HC. Siegl PKS. J. Cardiovasc. Pharmacol.  1987,  9:  246 
    Google Scholar
  • 14f Siegl PKS. Morgan G. Can. J. Physiol. Pharmacol.  1987,  65:  146 
    Google Scholar
  • 14g Siegl PKS. Wenger HC. Sweet CS. J. Cardiovasc. Pharmacol.  1984,  6:  565 
    Google Scholar
  • 15a Levy S. Metge M. Hilaire J. Cointe R. Bru P. Eychenne JL. Grerard R. Eur. Heart J.  1987,  8:  1236 
    Google Scholar
  • 15b Tryba M. Zenz M. Arzneim.-Forsch. (Drug Res.)  1987,  37:  1298 
    Google Scholar
  • 15c Jost S. Schulz W. Kober G. Arzneim.-Forsch. (Drug Res.)  1985,  35 (II):  1279 
    Google Scholar
  • 15d Herzog H. Simon H. Herz-Kreislauf  1983,  7:  354 
    Google Scholar
  • 15e Gulker H. Eur. Heart J.  1987,  8 (Suppl. L):  141 
    Google Scholar
  • 15f Gilfrich HJ. Oberhoffer M. Witzke J. Eur. Heart J.  1987,  8 (Suppl. L):  147 
    Google Scholar
  • 15g Hilaire J. Broustet JP. Colle JP. Theron M. Br. J. Clin. Pharmacol.  1983,  16:  627 
    Google Scholar
  • 16 Siegl PKS. Morgan G. Can. J. Physiol. Pharmacol.  1987,  65:  146 
    CrossrefGoogle Scholar
  • 17 Nakasaki M. Yamagami K. Isoe S. Bull. Chem. Soc. Jpn.  1961,  34:  1189 
    CrossrefGoogle Scholar
  • 18 Lipshutz BH. Liu Z.-P. Kayser F. Tetrahedron Lett.  1994,  35:  5567 
    CrossrefGoogle Scholar
  • 19 Dai-Ho G. Mariano PS. J. Org. Chem.  1987,  52:  704 
    CrossrefGoogle Scholar
  • 20 Chauncey DM. Andrews LJ. Keefer RM. J. Am. Chem. Soc.  1974,  96:  1850 
    CrossrefGoogle Scholar
  • 21 Olivera R. SanMartin R. Dominguez E. Solans X. Urtiaga MK. Arriortua MI. J. Org. Chem.  2000,  65:  6398 
    CrossrefGoogle Scholar
  • 22 Markaryan EA. Markaryan RE. Arustamyan ZS. Airepetyan GK. Sukasyan RS. Markaryan KZ. Asatryan TO. Pharm. Chem. J.  1997,  31:  13 
    Google Scholar
  • 23 Lu Y. Taylor RT. Heterocycles  2004,  62:  869 
    CrossrefGoogle Scholar
  • 24 Murata K. Bull. Chem. Soc. Jpn.  1973,  46:  1752 
    CrossrefGoogle Scholar