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Serotonin 5-HT6 receptor antagonists. II. Synthesis and structure—activity relationship of 3-arylsulfonyl-2-methylthiopyrazolo[1,5-a]pyrimidines with substituents containing an amine in the 6-position

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Pharmaceutical Chemistry Journal Aims and scope

3-(Arylsulfonyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidines containing substituents with an amine in the 6-position were synthesized. Their structure—activity (antagonist) relationship was studied with respect to serotonin 5-HT6 receptors. It was shown that 2-(methylthio)-3-(phenylsulfonyl)- and 2-(methylthio)-3-(3-chlorophenylsulfonyl)pyrazolo[1,5-a]pyrimidin-6-amines, the activity of which was comparable with 3-(arylsulfonyl)-2-(methylamino)pyrazolo[1,5-a]pyrimidin-6-amines and 3-(arylsulfonyl)-2-(methylamino)-and 3-(arylsulfonyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidin-7-amines that were reported earlier, were the most active picomolar ligands.

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References

  1. F. J. Monsma, Y. Shen, R. P. Ward, et al., Mol. Pharmacol., 43, 320–327 (1993).

    PubMed  CAS  Google Scholar 

  2. C. D. Unsworth and P. B. Molinoff, J. Pharmacol. Exp. Ther., 269, 246–255 (1994).

    CAS  Google Scholar 

  3. R. Kohen, M. A. Metcalf, N. Khan, et al., J. Neurochem., 66, 47–56 (1996).

    Article  PubMed  CAS  Google Scholar 

  4. R. A. Glennon, J. Med. Chem., 46, 2795–2812 (2003).

    Article  PubMed  CAS  Google Scholar 

  5. D. Macauley, American Chemical Society, 239th National Meeting, Investigating New Therapeutic Candidates, Part I, 21 – 25, March 2010, San Francisco, CA, USA; Drugs, 13(5), 289–291 (2010).

  6. http://www.avineuro.com/avineuro-pharmaceuticals-inc-reports-positive-phase-i-clinical-trial-results-on-avn-322-potent-small-molecule-for-treatment-of-alzheimer%e2%80%99s-disease/ (date of access, 4/13/2011).

  7. Thomson Reuters Drug News. Dec. 1, 2009. Lu AE58054 added to donepezil for the treatment of moderate Alzheimer’s disease (NCT01019421) ClinicalTrials.gov Web Site 2009, November 30.

  8. http://www.avineuro.com/avineuro-pharmaceuticals-inc-reports-positive-phase-2a-clinical-proof-of-concept-trial-results-on-avn-211-potent-small-molecule-for-treatment-of-schizophrenia (data of access, 4/13/2011).

  9. G. Maher-Edwards, R. Dixon, J. Hunter, et al., Int. J. Geriatr. Psychiatry, 24 Sep. (2010), DOI: 10.1002/gps.2562.

  10. http://www.lundbeck.com/investor/releases/ReleaseDetails/Release1412413EN.asp [http://investor.lundbeck.com/releasedetail.cfm?ReleaseID=677436] (date of access, 4/13/2011).

  11. A. J. Sleight, F. G. Boess, M. Bos, et al., Br. J. Pharmacol., 124, 556–562 (1998).

    Article  PubMed  CAS  Google Scholar 

  12. Y. Tsai, M. Dukat, A. Slassi, et al., Bioorg. Med. Chem. Lett., 10, 2295–2299 (2000).

    Article  PubMed  CAS  Google Scholar 

  13. R. A. Glennon, M. Lee, J. B. Rangisetty, et al., J. Med. Chem., 43, 1011–1018 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. J. Holenz, P. J. Pauwels, J. L. Diaz, et al., Drug Discovery Today, 11, No. 7/8, 283–299 (2006).

    Article  PubMed  CAS  Google Scholar 

  15. K. G. Liu and A. J. Robichaud, Drug Dev. Res., 70, 145–168 (2009).

    Article  CAS  Google Scholar 

  16. S. L. Davies, Drugs Future, 30, 479–495 (2005).

    Article  CAS  Google Scholar 

  17. D. J. Heal, S. L. Smith, A. Fisas, et al., Pharmacol. Ther., 117, 207–231 (2008).

    Article  PubMed  CAS  Google Scholar 

  18. A. V. Ivachtchenko, Y. A. Ivanenkov, and S. E. Tkachenko, Expert Opin. Ther. Pat., 20, 1171–1196 (2010).

    Article  PubMed  CAS  Google Scholar 

  19. M. L. Lopez-Rodrigues, B. Benhamu, T. de la Fuente, et al., J. Med. Chem., 48, 4216–4219 (2005).

    Article  Google Scholar 

  20. W. J. Geldenhuys and C. G. Van der Schyf, Curr. Top. Med. Chem., 8, 1035–1048 (2008).

    Article  PubMed  CAS  Google Scholar 

  21. W. D. Hirst, 33rd Annu. Meet. Soc. Neurosci., Nov. 8 – 12, New Orleans (2003).

  22. J. Berger, R. D. Clark, and S.-H. Zhao, WO / 2003 / 095434 (2003); http://www.wipo.int/pctdb/en/wo.jsp?WO=2003095434&IA=EP2003004671&DISPLAY=STATUS (accessed, 10/26/2010).

  23. N. Upton, T. T. Chuang, A. J. Hunter, and D. J. Virley, Neurotherapeutics, 5, 458–469 (2008).

    Article  PubMed  CAS  Google Scholar 

  24. M. Boes, C. Riemer, and H. Stadler, Eur. Pat. Appl. EP941994 (1999).

  25. S.-H. Zhao, J. Berger, R. D. Clark, et al., Bioorg. Med. Chem. Lett., 17, 3504–3507 (2007).

    Article  PubMed  CAS  Google Scholar 

  26. A. V. Ivachtchenko, D. E. Dmitriev, E. S. Golovina, et al., Bioorg. Med. Chem. Lett., 20, 2133–2136 (2010).

    Article  PubMed  CAS  Google Scholar 

  27. A. V. Ivachtchenko, E. S. Golovina, M. G. Kadieva, et al., Eur. J. Med. Chem., 46, 1189–1197 (2011).

    Article  PubMed  CAS  Google Scholar 

  28. A. V. Ivachtchenko, E. S. Golovina, M. G. Kadieva, et al., Bioorg. Med. Chem., 19, 1482–1491 (2011).

    Article  PubMed  CAS  Google Scholar 

  29. A. V. Ivachtchenko, D. E. Dmitriev, E. S. Golovina, et al., J. Med. Chem., 53, 5186–5196 (2010).

    Article  PubMed  CAS  Google Scholar 

  30. M. R. Pullagurla, T. Bondareva, R. Young, and R. A. Glennon, Bioorg. Med. Chem. Lett., 5298–5302 (2005).

  31. Y. Cheng and W. H. Prusoff, Biochem. Pharmacol., 22, 3099–3108 (1973).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Chemical Diversity Research Institute, Khimki, Moscow Oblast, 141401, Russia

    A. V. Ivachtchenko, E. S. Golovina, M. G. Kadieva & O. D. Mitkin

  2. ChemDiv Inc., 6605 Nancy Ridge Drive, San Diego, CA, 92121, United States

    A. V. Ivachtchenko, V. M. Kysil & I. M. Okun

Authors
  1. A. V. Ivachtchenko
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  2. E. S. Golovina
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  3. M. G. Kadieva
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  4. V. M. Kysil
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  5. O. D. Mitkin
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  6. I. M. Okun
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Correspondence to A. V. Ivachtchenko.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 46, No. 6, pp. 14 – 22, June, 2012.

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Ivachtchenko, A.V., Golovina, E.S., Kadieva, M.G. et al. Serotonin 5-HT6 receptor antagonists. II. Synthesis and structure—activity relationship of 3-arylsulfonyl-2-methylthiopyrazolo[1,5-a]pyrimidines with substituents containing an amine in the 6-position. Pharm Chem J 46, 337–345 (2012). https://doi.org/10.1007/s11094-012-0794-0

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  • DOI: https://doi.org/10.1007/s11094-012-0794-0

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