Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH18510
RESEARCH ARTICLE
Contents Vol 72(3)

In Pursuit of Fluorinated Sigma Receptor Ligand Candidates Related to [18F]-FPS*

Rasha S. Jwad A B , Alan H. C. Pang A , Luke Hunter A and Roger W. Read A C
+ Author Affiliations
- Author Affiliations

A School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia.

B Department of Chemistry, College of Science, Al-Nahrain University, Al-Jadriya, Baghdad 10070, Iraq.

C Corresponding author. Email: r.read@unsw.edu.au

Australian Journal of Chemistry 72(3) 213-225 https://doi.org/10.1071/CH18510
Submitted: 19 October 2018  Accepted: 19 November 2018   Published: 10 December 2018

Abstract

This paper describes the synthesis of N-arylmethyl(1-benzyl) and N-aroyl(1-benzoyl) 4-(4-fluoromethylphenoxymethyl)piperidines as potential sigma receptor ligands analogous to the potent and highly selective sigma-1 ligand [18F]-FPS, but with enhanced or alternative binding and transport profiles. The synthesis involves N-aroylation of 4-hydroxmethylpiperidine or ethyl nipecotate, functional group manipulation of the ester group or simple activation of the hydroxyl group to introduce the phenoxy component, and subsequent functional group manipulation to reduce the amide group and introduce the fluorine into the fluoromethyl substituent. In its development, the synthesis was found to require early N-aroylation of the piperidine precursor to avoid complications due to anchimeric assistance by its nitrogen in subsequent displacement reactions. New evidence is presented on the pathway followed in a literature report of direct displacement of a benzylic hydroxyl group by fluoride ion under Appel-like conditions. Relevant to the literature report, the halide ion in the fluoromethylphenoxy 1-benzylpiperidine derivatives was surprisingly labile to hydrolytic displacement on chromatography and this aspect is worthy of further study. Moreover, the NMR spectra of the amides were complicated by geometric isomerism about the amide C(O)–N bond, but detailed analysis of spectra from 2-anisoyl derivatives allowed the assignment of diastereomeric contributors to consistent, secondary atropisomerism about the aryl–C(O) bond.


References

[1]  K. Kawamura, H. Tsukada, K. Shiba, C. Tsuji, N. Harada, Y. Kimura, K. Ishiwata, Nucl. Med. Biol. 2007, 34, 571.
         | Crossref | GoogleScholarGoogle Scholar |

[2]  D. J. Rowland, Z. Tue, J. Xu, D. Ponde, R. H. Mach, M. J. Welch, J. Nucl. Med. 2006, 47, 1041.

[3]  J. L. Musachio, U. Scheffel, M. Stathis, H. T. Ravert, W. B. Mathews, R. F. Dannals, Life Sci. 1994, 55, PL225.
         | Crossref | GoogleScholarGoogle Scholar |

[4]  R. N. Waterhouse, R. C. Chang, N. Atuehene, T. L. Collier, Synapse 2007, 61, 540.
         | Crossref | GoogleScholarGoogle Scholar |

[5]  W. D. Bowen, Pharm. Acta Helv. 2000, 74, 211.
         | Crossref | GoogleScholarGoogle Scholar |

[6]  J. E. Bermack, G. Debonnel, J. Pharmacol. Sci. 2005, 97, 317.
         | Crossref | GoogleScholarGoogle Scholar |

[7]  T. Hayashi, T. P. Su, CNS Drugs 2004, 18, 269.
         | Crossref | GoogleScholarGoogle Scholar |

[8]  B. J. Vilner, C. S. John, W. D. Bowen, Cancer Res. 1995, 55, 408.

[9]  T. L. Collier, R. N. Waterhouse, M. Kassiou, Curr. Pharm. Des. 2007, 13, 51.
         | Crossref | GoogleScholarGoogle Scholar |

[10]  M. Manohar, S. D. Banister, C. Beinat, J. O’Brien-Brown, M. Kassiou, Aust. J. Chem. 2015, 68, 600.
         | Crossref | GoogleScholarGoogle Scholar |

[11]  D. Y. Maeda, W. Williams, W. E. Kim, L. N. Thatcher, W. D. Bowen, A. Coop, Bioorg. Med. Chem. Lett. 2002, 12, 497.
         | Crossref | GoogleScholarGoogle Scholar |

[12]  H. Takahashi, J. R. Kirsch, K. Hasimoto, E. D. London, R. C. Koehler, R. J. Traystman, Stroke 1995, 26, 1676.
         | Crossref | GoogleScholarGoogle Scholar |

[13]  H. Takahashi, J. R. Kirsch, K. Hasimoto, E. D. London, R. C. Koehler, R. J. Traystman, Stroke 1996, 27, 2120.
         | Crossref | GoogleScholarGoogle Scholar |

[14]  T. Goyagi, S. Goto, A. Bhardwaj, V. L. Dawson, P. D. Hurn, J. R. Kirsch, Stroke 2001, 32, 1613.
         | Crossref | GoogleScholarGoogle Scholar |

[15]  A. Foster, H. Wu, W. Chen, W. Williams, W. D. Bowen, R. R. Matsumoto, A. Coop, Bioorg. Med. Chem. Lett. 2003, 13, 749.
         | Crossref | GoogleScholarGoogle Scholar |

[16]  T. M. Gund, J. Floyd, D. Jung, J. Mol. Graph. Model. 2004, 22, 221.
         | Crossref | GoogleScholarGoogle Scholar |

[17]  R. A. Glennon, S. Y. Ablordeppey, A. M. Ismaiel, M. B. El-Ashmawy, J. B. Fischer, K. B. Howie, J. Med. Chem. 1994, 37, 1214.
         | Crossref | GoogleScholarGoogle Scholar |

[18]  P. Cratteri, M. N. Romanelli, G. Cruciani, C. Bonaccini, F. Melani, J. Comput. Aided Mol. Des. 2004, 18, 361.
         | Crossref | GoogleScholarGoogle Scholar |

[19]  S. Y. Ablordeppey, J. B. Fischer, R. A. Glennon, Bioorg. Med. Chem. 2000, 8, 2105.
         | Crossref | GoogleScholarGoogle Scholar |

[20]  T. L. Collier, J. C. O’Brien, R. N. Waterhouse, J. Labelled Comp. Radiopharm. 1996, 38, 785.
         | Crossref | GoogleScholarGoogle Scholar |

[21]  R. N. Waterhouse, M. Slifstein, P. Talbot, A. Sultana, Y. Sudo, M. Laruelle, Neuroimage 2002, 16, S6.

[22]  R. N. Waterhouse, K. Mardon, J. C. O’Brien, Nucl. Med. Biol. 1997, 24, 45.
         | Crossref | GoogleScholarGoogle Scholar |

[23]  B. P. Bandgar, V. T. Kamble, A. V. Biradar, Monatsh. Chem. 2005, 136, 1579.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  M. Rupprich, C. Decristoforo, B. Matuszczak, Monatsh. Chem. 2009, 140, 405.
         | Crossref | GoogleScholarGoogle Scholar |

[25]  P. Hernández, A. Merlino, A. Gerpe, W. Porcal, O. E. Piro, M. González, H. Cerecettoa, ARKIVOC 2006, 6, 128.

[26]  T. Wang, Y.-H. Zhang, X.-W. Kong, Y.-S. Lai, H. Ji, Y.-P. Chen, S.-X. Peng, Chem. Biodivers. 2009, 6, 466.
         | Crossref | GoogleScholarGoogle Scholar |

[27]  C. Lecoutey, C. Rochais, D. Genest, S. Butt-Guelle, C. Ballandonne, S. Corvaisier, F. Dulin, A. Lepailleur, J. Sopkova-de Oliveira Santos, P. Dallemagne, MedChemComm 2012, 3, 627.
         | Crossref | GoogleScholarGoogle Scholar |

[28]  K. S. T. Dias, C. T. de Paul, T. dos Santos, I. N. O. Souza, M. S. Boni, M. J. R. Guimarães, F. M. R. da Silva, N. G. Castro, G. A. Neves, C. C. Veloso, M. M. Coelho, I. S. F. de Melo, F. C. V. Giusti, A. Giusti-Paiva, M. L. da Silva, L. E. Dardenne, I. A. Guedes, L. Pruccoli, F. Morroni, A. Tarozzi, C. Viegas, Eur. J. Med. Chem. 2017, 130, 440.
         | Crossref | GoogleScholarGoogle Scholar |

[29]  J. A. Hirsch, R. L. Augustine, G. Koletar, H. G. Wolf, J. Org. Chem. 1975, 40, 3547.
         | Crossref | GoogleScholarGoogle Scholar |

[30]  M. Tafazzoli, A. Ziyaei–Halimjani, M. Ghiasi, M. Fattahi, M. R. Saidi, J. Mol. Struct. 2008, 886, 24.
         | Crossref | GoogleScholarGoogle Scholar |

[31]  E. Kumarasamy, R. Raghunathan, M. P. Sibi, J. Sivaguru, Chem. Rev. 2015, 115, 11239.
         | Crossref | GoogleScholarGoogle Scholar |

[32]  O. Mitsunobu, Synthesis 1981, 1.
         | Crossref | GoogleScholarGoogle Scholar |

[33]  A. W. Williamson, Q. J. Chem. Soc. Lond. 1852, 4, 229.
         | Crossref | GoogleScholarGoogle Scholar |

[34]  M. Y. Lee, D. J. Baek, S. Lee, D. Kim, S. Kim, J. Org. Chem. 2011, 76, 408.
         | Crossref | GoogleScholarGoogle Scholar |

[35]  G. R. Fulmer, A. J. M. Miller, N. H. Sherden, H. E. Gottlieb, A. Nudelman, B. M. Stoltz, J. E. Bercaw, K. I. Goldberg, Organometallics 2010, 29, 2176.
         | Crossref | GoogleScholarGoogle Scholar |

[36]  C. F. Koelsch, J. Am. Chem. Soc. 1944, 66, 1611.
         | Crossref | GoogleScholarGoogle Scholar |

[37]  P. R. Bovy, G. Courtemanche, O. Crespin, PCT Int. Appl., WO 2001064671 A2 20010907 2001.

[38]  G. Courtemanche, O. Crespin, C. Pascal, PCT Int. Appl., WO 2001064631 A2 20010907 2001.

[39]  G. Courtemanche, O. Crespin, C. Pascal, PCT Int. Appl. (), WO 2002006272 A1 20020124 2002.

[40]  J. Bertin, P. R. Bovy, G. Courtemanche, O. Crespin, G. Defosse, E. Fett, PCT Int. Appl. WO 2000046220 A1 20000810 2000.

[41]  C. Lecoutey, C. Rochais, D. Genest, S. Butt-Gueulle, C. Ballandonne, S. Corvaisier, F. Dulin, A. Lepailleur, J. Sopkova-de Oliviera Santos, P. Dallemagne, MedChemComm 2012, 3, 627.
         | Crossref | GoogleScholarGoogle Scholar |

[42]  K. S. T. Dias, C. T. de Paula, T. dos Santos, I. N. O. Souza, M. S. Boni, M. J. R. Guimaraes, F. M. R. da Silva, N. G. Casstro, G. A. Neves, C. C. Veloso, M. M. Coelho, I. S. F. de Melo, F. C. V. Giusti, A. Giusti-Paiva, M. L. da Silva, L. E. Dardenne, I. A. Guedes, L. Pruccoli, F. Morroni, A. Tarozzi, C. Viegas, Eur. J. Med. Chem. 2017, 130, 440.
         | Crossref | GoogleScholarGoogle Scholar |

[43]  F. Rancati, A. Rizzi, L. Carzaniga, I. Linney, C. Knight, W. Schmidt, PCT Int. Appl., WO 2018011090 A1 20180118 2018.

[44]  T. W. Bentley, M. Christi, R. Kemmer, G. Llewellyn, J. E. Oakley, J. Chem. Soc., Perkin Trans. 2 1994, 2531.
         | Crossref | GoogleScholarGoogle Scholar |

[45]  J. Dong, L. Krasnova, M. G. Finn, K. B. Sharpless, Angew. Chem. Int. Ed. 2014, 53, 9430.
         | Crossref | GoogleScholarGoogle Scholar |

[46]  S. Bloom, C. R. Pitts, R. Woltornist, A. Griswold, M. G. Holl, T. Lectka, Org. Lett. 2013, 15, 1722.
         | Crossref | GoogleScholarGoogle Scholar |

[47]  Y. Amaoka, M. Nagatomo, M. Inoue, Org. Lett. 2013, 15, 2160.
         | Crossref | GoogleScholarGoogle Scholar |

[48]  K. B. McMurtrey, J. M. Racowski, M. S. Sanford, Org. Lett. 2012, 14, 4094.
         | Crossref | GoogleScholarGoogle Scholar |

[49]  W. Liu, X. Huang, M.-J. Cheng, R. J. Nielsen, W. A. Goddard, J. T. Groves, Science 2012, 337, 1322.
         | Crossref | GoogleScholarGoogle Scholar |

[50]  W. Liu, X. Huang, J. T. Groves, Nat. Protoc. 2013, 8, 2348.
         | Crossref | GoogleScholarGoogle Scholar |

[51]  W. Liu, J. T. Groves, Angew. Chem. Int. Ed. 2013, 52, 6024.
         | Crossref | GoogleScholarGoogle Scholar |

[52]  X. Huang, W. Liu, H. Ren, R. Neelamegam, J. M. Hooker, J. T. Groves, J. Am. Chem. Soc. 2014, 136, 6842.
         | Crossref | GoogleScholarGoogle Scholar |

[53]  A. Rentmeister, F. H. Arnold, R. Fasan, Nat. Chem. Biol. 2009, 5, 26.
         | Crossref | GoogleScholarGoogle Scholar |

[54]  G. R. Fulmer, A. J. M. Miller, N. H. Sherden, H. E. Gottlieb, A. Nudelman, B. M. Stoltz, J. E. Bercaw, K. I. Goldberg, Organometallics 2010, 29, 2176.
         | Crossref | GoogleScholarGoogle Scholar |

[55]  R. K. Harris, E. D. Becker, S. M. Cabral De Menezes, P. Granger, R. E. Hoffman, K. Zilm, Pure Appl. Chem. 2008, 80, 59.
         | Crossref | GoogleScholarGoogle Scholar |

[56]  C. P. Rosenau, B. J. Jelier, A. D. Gossert, A. Togni, Angew. Chem. Int. Ed. 2018, 57, 9528.
         | Crossref | GoogleScholarGoogle Scholar |