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Synthesis of aryl-substituted or aryl-fused N-hydroxyethyl and N-hydroxymethypyrazole derivatives as potential ligands for the estrogen receptor

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Abstract

A new series of N-hydroxyethylpyrazole (12a–f) and N-hydroxymethylpyrazole derivatives (15a–f) were designed for their estrogenic activities, having a 11.0 ± 0.5 Å distance between their two hydroxyl groups, aliphatic–OH and phenolic–OH similar to 17β-estradiol (E2) as an endogenous hormone. To synthesize the title compounds, the key intermediate 1,3-dicarbonyl derivatives (2 and 8), were treated with hydrazine hydrate to produce the pyrazole ring 5 and 9. Further hydroxyalkylation of the latter produced the title pyrazoles. The position of hydroxyethyl or hydroxymethyl substituents in the products was determined through 2D NOE NMR spectroscopy.

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References

  1. S.W. Landvatter, J.A. Katzenellenbogen, J. Med. Chem. 25, 1300 (1982)

    Article  CAS  Google Scholar 

  2. S. Bertini, A. De Cupertinis, C. Granchi, B. Bargagli, T. Tuccinardi, A. Martinelli, M. Macchia, J.R. Gunther, K.E. Carlson, J.A. Katzenellenbogen, F. Minutolo, Eur. J. Med. Chem. 46, 2453 (2011)

    Article  CAS  Google Scholar 

  3. R.E. McDevitt, M.S. Malamas, E.S. Manas, R.J. Unwalla, Z.B. Xu, C.P. Miller, H.A. Harris, Bioorg. Med. Chem. Lett. 15, 3137 (2005)

    Article  CAS  Google Scholar 

  4. M. Waibel, K.J. Kieser, K.E. Carlson, F. Stossi, B.S. Katzenellenbogen, J.A. Katzenellenbogen, Eur. J. Med. Chem. 44, 3560 (2009)

    Article  CAS  Google Scholar 

  5. R.A. Magarian, L.B. Overaacre, S. Singh, Curr. Med. Chem. 1, 61 (1994)

    CAS  Google Scholar 

  6. J. Grundy, Chem. Rev. 57, 281 (1957)

    Article  CAS  Google Scholar 

  7. D.R. Compton, K.E. Carlson, J.A. Katzenellenbogen, Bioorg. Med. Chem. Lett. 14, 5681 (2004)

    Article  CAS  Google Scholar 

  8. M. Shekarchi, M. Pirali-Hamedani, L. Navidpour, N. Adib, A. Shafiee, J. Iran. Chem. Soc. 5, 150 (2008)

    Article  CAS  Google Scholar 

  9. S.R. Stauffer, C.J. Coletta, R. Tedesco, G. Nishigushi, K. Carlson, J. Sun, B.S. Katzenellenbogen, J.A. Katzenellenbogan, J. Med. Chem. 43, 4934 (2000)

    Article  CAS  Google Scholar 

  10. B.E. Fink, D.S. Mortensen, S.R. Stauffer, Z.D. Aron, J.A. Katzenellenbogen, Chem. Biol. 6, 205 (1999)

    Article  CAS  Google Scholar 

  11. S.R. Stauffer, Y.R. Huang, Z.D. Aron, C.J. Coletta, J. Sun, B.S. Katzenellenbogen, J.A. Katzenellenbogen, Bioorg. Med. Chem. 9, 151 (2001)

    Article  CAS  Google Scholar 

  12. X. Alexi, K.M. Kasiotis, N. Fokialakis, G. Lambrinidis, A.K. meligova, E. Mikros, S.A. Haroutounian, M.N. Alexis. J. steroid Biochem. Mol. Biol. 117, 159 (2009)

    Article  CAS  Google Scholar 

  13. J.S. Wright, H. Shadnia, J.M. Anderson, J.M. Anderson, J.M. Anderson, T. Durst, M. Assim, M. El-salfiti, C. Choueiri, M.A.C. Pratt, S.C. Ruddy, R. Lau, K.E. Carlson, J.A. Katzenellenbogen, P.J. O’Brien, L. Wan, J. Med. Chem. 54, 433 (2011)

    Article  CAS  Google Scholar 

  14. N. Minami, Y. Suzuki, Yakugaku Zasshi 95, 815 (1975)

    CAS  Google Scholar 

  15. M.T. Di Parsia, C. Suarez, M.J. Vitolo, V.E. Marquez, J. Med. Chem. 24, 117 (1981)

    Article  Google Scholar 

  16. E.C. Taylor, A. Mc Killop, Y. Shvo, G.H. Hawks, Tetrahedron 23, 2081 (1967)

    Article  CAS  Google Scholar 

  17. J.G. Morgan, K. Darrell Berlin, N.N. Durham, R.W. Chesnut, J. Heterocycl. Chem. 8, 61 (1971)

    Article  CAS  Google Scholar 

  18. J.A. may, P.W. Zinke, US Pat., 2003, 2003/83346

  19. Z.-F. Tao, G, Li, Y. Tong, Z. Chen, P. Merta, P. Kovar, H. Zhang, S.H. Rosenberg, H.L. Sham, T.J. Sowin, N.-H. Lin, Bioorg. Med. Chem. Lett. 17, 4308 (2007)

    Article  CAS  Google Scholar 

  20. V.K. Aggarwal, J. de Vicente, R.V. Bonnert, J. Org. Chem. 68, 5381 (2003)

    Article  CAS  Google Scholar 

  21. L. Levi, C. Boersch, C.F. Gers, E. Merkul, T.J.J. Müller, Molecules 16, 9340 (2011)

    Article  CAS  Google Scholar 

  22. C.J. Valduga, H.S. Braibante, M.E.F. Braibante, J. Heterocycl. Chem. 34, 1453 (1997)

    Article  CAS  Google Scholar 

  23. R.G. Parker, J.D. Roberts, J. Org. Chem. 35, 996 (1970)

    Article  CAS  Google Scholar 

  24. S. Sivaprasad, R. Sridhar, P.T. Perumal, J. Heterocycl. Chem. 43, 389 (2006)

    Article  CAS  Google Scholar 

  25. A.O. Baltayan, V.I. Rstakyan, S.K. Antanosyan, F.S. Kinoyan, O.S. Attaryan, G.V. Asratyan, Russ. J. Gen. Chem. 79, 2417 (2009)

    Article  CAS  Google Scholar 

  26. K.M. Kasiotis, N. Fokialakis, S.A. Haroutounian, Synthesis 11, 1791 (2006)

    Google Scholar 

  27. A.R. Katritzky, P. Lue, K. Akutagawa, Tetrahedron 45, 4253 (1989)

    Article  CAS  Google Scholar 

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Acknowledgments

This research was supported by a grant from National Elite Foundation.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, 14176, Tehran, Iran

    Maryam Allahyari-Devin, Behnam Abedi, Latifeh Navidpour & Abbas Shafiee

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  1. Maryam Allahyari-Devin
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  2. Behnam Abedi
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  3. Latifeh Navidpour
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  4. Abbas Shafiee
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Correspondence to Latifeh Navidpour or Abbas Shafiee.

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Allahyari-Devin, M., Abedi, B., Navidpour, L. et al. Synthesis of aryl-substituted or aryl-fused N-hydroxyethyl and N-hydroxymethypyrazole derivatives as potential ligands for the estrogen receptor. J IRAN CHEM SOC 10, 43–53 (2013). https://doi.org/10.1007/s13738-012-0126-z

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  • DOI: https://doi.org/10.1007/s13738-012-0126-z

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