Advertisement

Insights in Organometallic Synthesis of Various Adamantane Derivatives with Sigma Receptor-Binding Affinity and Antiproliferative/Anticancer Activity

  • Ioannis Papanastasiou
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1824)

Abstract

Organometallic reactions, such as those involving Grignard and organocadmium reagents, are very useful but require prudent laboratory skills. In many papers related to the medicinal chemistry of adamantane derivatives with sigma receptor (σR)-binding affinity and antiproliferative/anticancer activity, organometallics play a crucial role in the synthetic pathways. In this work, the experimental procedures utilizing Grignard and organocadmium reagents are presented in detail, because these techniques are not analyzed and are important in the rational drug design.

Key words

Adamantane derivatives Sigma receptor Organocadmium reaction Grignard reaction 

References

  1. 1.
    Wanka L, Iqbal K, Schreiner PR (2013) The lipophilic bullet hits the targets: medicinal chemistry of adamantane derivatives. Chem Rev 113(5):3516–3604. https://doi.org/10.1021/cr100264t CrossRefGoogle Scholar
  2. 2.
    Spilovsk K, Zemek F, Korabecny J et al (2016) Adamantane – a lead structure for drugs in clinical practice. Curr Med Chem 23(29):3245–3266. https://doi.org/10.2174/0929867323666160525114026 CrossRefGoogle Scholar
  3. 3.
    Narayanan S, Bhat R, Mesangeau C et al (2010) Early development of sigma-receptor ligands. Fut Med Chem 3(1):79–94. https://doi.org/10.4155/fmc.10.279 CrossRefGoogle Scholar
  4. 4.
    Akhtar MJ, Ahamed M, Alhadlaq HA et al (2014) Targeted anticancer therapy: overexpressed receptors and nanotechnology. Clin Chim Acta 436:78–92CrossRefGoogle Scholar
  5. 5.
    Van Waarde A, Rybczynska AA, Ramakrishnan NK et al (2015) Potential applications for sigma receptor ligands in cancer diagnosis and therapy. Biochim Biophys Acta 1848(10):2703–2714. https://doi.org/10.1016/j.bbamem.2014.08.022 CrossRefGoogle Scholar
  6. 6.
    Kornhuber J, Schoppmeyer K, Riederer P (1993) Affinity of 1-amino- adamantanes for the binding site in post-mortem human frontal cortex. Neurosci Lett 163(2):129–131. https://doi.org/10.1016/0304-3940(93)90362-O CrossRefGoogle Scholar
  7. 7.
    Ronsisvalle G, Marrazzo A, Prezzavento O et al (2000) Substituted 1-phenyl-2-cyclopropyl-methylamines with high affinity and selectivity for sigma sites. Bioorg Med Chem 8(6):1503–1513. https://doi.org/10.1016/S0968-0896(00)00072-9 CrossRefGoogle Scholar
  8. 8.
    Bourrie B, Bribes E, De Nys N et al (2002) SSR125329A, a high affinity sigma receptor ligand with potent anti-inflammatory properties. Eur J Pharmacol 456:123–131. https://doi.org/10.1016/S0014-2999(02)02646-8 CrossRefGoogle Scholar
  9. 9.
    Bucolo C, Marrazzo A, Ronsisvalle S et al (2006) A novel adamantane derivative attenuates retinal ischemia–reperfusion damage in the rat retina through σ1 receptors. Eur J Pharmacol 536:200–203. https://doi.org/10.1016/j.ejphar.2006.02.026 CrossRefGoogle Scholar
  10. 10.
    Banister SD, Yoo DT, Wern Chua S et al (2011) N-Arylalkyl-2-azaadamantanes as cage-expanded polycarbocyclic sigma (σ) receptor ligands. Bioorg Med Chem Lett 21:5289–5292. https://doi.org/10.1016/j.bmcl.2011.07.028 CrossRefGoogle Scholar
  11. 11.
    Riganas S, Papanastasiou I, Foscolos GB et al (2012) New adamantane phenylalkylamines with σ-receptor binding affinity and anticancer activity, associated with putative antagonism of neuropathic pain. J Med Chem 55:10241–10261. https://doi.org/10.1021/jm3013008 CrossRefGoogle Scholar
  12. 12.
    Riganas S, Papanastasiou I, Foscolos GB et al (2012) Synthesis, σ1, σ2-receptors binding affinity and antiproliferative action of new C1-substituted adamantanes. Bioorg Med Chem 20:3323–3331. https://doi.org/10.1016/j.bmc.2012.03.038 CrossRefGoogle Scholar
  13. 13.
    Riganas S, Papanastasiou I, Foscolos GB et al (2012) New adamantane derivatives with sigma affinity and antiproliferative activity. Med Chem 8:569–586. https://doi.org/10.2174/157340612801216201 CrossRefGoogle Scholar
  14. 14.
    Fytas C, Zoidis G, Tsotinis A et al (2015) Novel 1-(2-aryl-2-adamantyl)piperazine derivatives with antiproliferative activity. Eur J Med Chem 93:281–290. https://doi.org/10.1016/j.ejmech.2015.02.021 CrossRefGoogle Scholar
  15. 15.
    Fytas G, Kolocouris N, Foscolos GB, Pouli N (1989) Aminoethers de quelques aryladamantanols. Chimika Chronika New Ser 18:47–57Google Scholar
  16. 16.
    Liu KT, Sheu HC (1991) Solvolysis of 2-aryl-2-chloroadamantanes. A new Y scale benzylic chlorides. J Org Chem 56(9):3021–3025. https://doi.org/10.1021/jo00009a018 CrossRefGoogle Scholar
  17. 17.
    Georgiadis M-O, Karoutzou O, Foscolos A-S, Papanastasiou I (2017) Sigma receptor (σR) ligands with antiproliferative and anticancer activity. Molecules 22(9):1408. https://doi.org/10.3390/molecules22091408 CrossRefGoogle Scholar
  18. 18.
    De Costa BR, He X (1994) Structure–activity relationships and evolution of σ receptor ligands. In: Itzhak Y (ed) Sigma receptors. Academic Press, London, pp 45–111Google Scholar
  19. 19.
    Papanastasiou I, Tsotinis A, Kolocouris N et al (2014) New aminoadamantane derivatives with antiproliferative activity. Med Chem Res 23:1966–1975. https://doi.org/10.1007/s00044-013-0798-7 CrossRefGoogle Scholar
  20. 20.
    Papanastasiou I, Riganas S, Foscolos GB et al (2015) Synthesis and cytotoxicity of 4-(2-Adamantyl)phenylalkylamines. Lett Org Chem 12(5):319–323. https://doi.org/10.2174/157017861205150509202419 CrossRefGoogle Scholar
  21. 21.
    Koperniku A, Foscolos A-S, Papanastasiou I et al (2016) 4-(1-Adamantyl)phenyl alkylamines with potential anti- proliferative activity. Lett Org Chem 13(3):171–176. https://doi.org/10.2174/1570178613666160104233856 CrossRefGoogle Scholar
  22. 22.
    Papaconstantinou-Garoufalias S, Foscolos GB, Costakis E (1984) Adamantane analogs of diphenhydramine. Chim Chron, New series, 13:225–237Google Scholar
  23. 23.
    Stetter H, Rauscher E (1960) Uber verbindungen mit urotropin-struktur XVII. Zur kenntnis der adamantan-carbosäure-(I). Chem Ber 93(5):1161–1166. https://doi.org/10.1002/cber.19600930527 CrossRefGoogle Scholar
  24. 24.
    Cason J (1947) The use of organocadmium reagents for the preparation of ketones. Chem Rev 40(1):15–32. https://doi.org/10.1021/cr60125a002 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical ChemistryNational and Kapodistrian University of Athens, Panepistimiopolis—ZografouAthensGreece

Personalised recommendations