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Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents

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Abstract

Considering the importance of hydantoin derivatives in treatment of status epilepticus, four 5-phenylhydantoins, whose lipophilicities were estimated to be similar to that of phenytoin, were synthesized. Evaluation of their anticonvulsant activities was performed on rats by subcutaneous pentylenetetrazol seizure test and intravenous pentylenetetrazol threshold test, and spontaneous locomotor activity test was used to assess possible sedative effects. X-ray analysis of three compounds suggested that certain analogies might be drawn between interactions in crystal packing and biological interactions responsible for their anticonvulsant activity. It was found that 5-ethyl-5-phenyl-3-propylhydantoin exhibits the most favorable pharmacological properties among the synthesized compounds, i.e., anticonvulsant activity comparable to phenytoin with lower liability for induction of sedation in rats.

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References

  1. Yaari Y, Selzer ME, Pincus JH (1986) Ann Neurol 20:171

    Article  CAS  Google Scholar 

  2. Danielsson BR, Skold AC, Azarbayjani F (2001) Curr Pharm Des 7:787

    Article  CAS  Google Scholar 

  3. Willow M, Kuenzel EA, Catterall WA (1984) Mol Pharmacol 25:228

    CAS  Google Scholar 

  4. Willow M, Gonoi T, Catterall WA (1985) Mol Pharmacol 27:549

    CAS  Google Scholar 

  5. Troupin AS, Friel P, Lovely MP, Wilensky AJ (1979) Ann Neurol 6:410

    Article  CAS  Google Scholar 

  6. Smythies JR (1980) Receptor modeling for anticonvulsant and convulsant drugs. In: Glaser GH, Penry JK, Kiffin J, Woodbury DM (eds) Advances in neurology, vol 27. Raven, New York, p 207

    Google Scholar 

  7. Trišović N, Valentić N, Erović M, Đaković–Sekulić T, Ušćumlić G, Juranić I (2011) Monatsh Chem 142:1227

  8. Scholl S, Koch A, Henning D, Kempter G, Kleinpeter E (1999) Struct Chem 10:355

    Article  CAS  Google Scholar 

  9. Zha C, Brown GB, Brouillette WJ (2004) J Med Chem 47:6519

    Article  CAS  Google Scholar 

  10. Camerman A, Camerman N (1971) Acta Crystallogr B27:2205

    Google Scholar 

  11. Brouillette WJ, Brown GB, DeLorey TM, Liang G (1990) J Pharm Sci 79:871

    Article  CAS  Google Scholar 

  12. Brown ML, Brown GB, Brouillette WJ (1997) J Med Chem 40:602

    Article  CAS  Google Scholar 

  13. Sechi G, Rosati G, Deiana GA, Petruzzi V, Deriu F, Correddu P, De Riu PL (1997) Brain Res 764:230

    Article  CAS  Google Scholar 

  14. Trinka E (2009) Epilepsia 50:40

    Article  Google Scholar 

  15. Lamberty Y, Klitgaard H (2000) Epilepsy Behav 1:256

    Article  Google Scholar 

  16. Dimmock JR, Puthucode RN, Smith JM, Hetherington M, Quail JW, Pugazhenthi U, Lechler T, Stables JP (1996) J Med Chem 39:3984

    Article  CAS  Google Scholar 

  17. Jones GP, Andrews PR (1987) J Chem Soc Perkin Trans 2 4:415–421

    Google Scholar 

  18. Bucherer HT, Lieb VA (1934) J Prakt Chem 141:5

    Article  CAS  Google Scholar 

  19. Suzuki H, Kneller MB, Rock DA, Jones JP, Trager WF, Rettie AE (2004) Arch Biochem Biophys 429:1

    Article  CAS  Google Scholar 

  20. Trišović N, Valentić N, Ušćumlić G (2011) Chem Cent J 5:62

    Article  Google Scholar 

  21. Fabrique de produits chimiques ci-devant Sandoz (1934) Therapeutic compounds. FR Patent 769,667, Aug 31, 1934; (1934) Chem Abstr 29:12252

  22. Kocer HB, Worley SD, Broughton RM, Acevedo O, Huang TS (2010) Ind Eng Chem Res 49:11188

    Article  CAS  Google Scholar 

  23. Altomare A, Cascarano G, Giacovazzo C, Guagliardi A, Burla MC, Polidori G, Camalli M (1994) J Appl Cryst 27:435

    Google Scholar 

  24. Sheldrick GM (2008) Acta Crystallogr A64:112

    CAS  Google Scholar 

  25. Farrugia LJ (1999) J Appl Crystallogr 32:837

    Article  CAS  Google Scholar 

  26. Mandhane SN, Aavula K, Rajamannar T (2007) Seizure 16:636

    Article  Google Scholar 

  27. Savić MM, Milinković MM, Rallapalli S, Clayton ST, Joksimović S, Van Linn M, Cook JM (2009) Int J Neuropsychopharmacol 12:1179

    Article  Google Scholar 

Download references

Acknowledgments

This work was performed within the framework of research project no. 172013 supported by the Ministry of Education and Science of the Republic of Serbia.

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Authors and Affiliations

  1. Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11000, Belgrade, Serbia

    Nemanja Trišović, Jelena Rogan, Dejan Poleti & Gordana Ušćumlić

  2. Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000, Belgrade, Serbia

    Tamara Timić, Jovana Divljaković & Miroslav M. Savić

Authors
  1. Nemanja Trišović
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  2. Tamara Timić
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  3. Jovana Divljaković
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  4. Jelena Rogan
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  6. Miroslav M. Savić
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  7. Gordana Ušćumlić
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Correspondence to Gordana Ušćumlić.

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Trišović, N., Timić, T., Divljaković, J. et al. Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents. Monatsh Chem 143, 1451–1457 (2012). https://doi.org/10.1007/s00706-012-0791-8

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  • DOI: https://doi.org/10.1007/s00706-012-0791-8

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