Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Anticonvulsant Activity of a Combined Pharmacophore of Pyrazolo-pyridines with Lesser Toxicity in Mice

  • Siddiqui, Nadeem (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University) ;
  • Ahsan, Waquar (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University) ;
  • Alam, M Shamsher (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University) ;
  • Ali, Ruhi (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University) ;
  • Srivastava, Kamna (Center for Biomedical Research, University of Delhi) ;
  • Ahmed, Sharique (Department of Biochemistry, Faculty of Medicine, 7th October University)
  • Received : 2010.10.25
  • Accepted : 2010.12.07
  • Published : 2011.02.20
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Abstract

Various 2-amino-6-[3-(substituted phenyl)-5-phenyl-4,5-dihydropyrazol-1-yl]-4-(substituted phenyl)nicotinonitriles (3a-t) were designed and synthesized by clubbing two active anticonvulsant pharmacophores pyrazole and pyridine. All the synthesized compounds possessed the pharmacophoric elements essential for good anticonvulsant activity. The anticonvulsant screening was performed by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. Two compounds 3i and 3s showed significant anticonvulsant activity in both the screens with $ED_{50}$ values 17.5 mg/kg and 22.6 mg/kg respectively in MES screen and 154.1 mg/kg and 242.6 mg/kg respectively in scPTZ screen. They were also found to have no acute toxic effects in mice when tested at elevated doses.

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References

  1. Ozdemir, Z.; Kandilci, H. B.; Gümüşel, B.; Caliş, U.; Bilgin, A. A. Eur. J. Med. Chem. 2007, 42, 373-379. https://doi.org/10.1016/j.ejmech.2006.09.006
  2. Ozdemir, Z.; Burak, K. H.; Gumusel, B.; Calis, U.; Altan, B. A. Arch. Pharm. 2008, 341, 701-707. https://doi.org/10.1002/ardp.200800068
  3. Abdel-Aziz, M.; El-Din, A. G.; Hassan, A. A. Eur. J. Med. Chem. 2001, 44, 3480-3487.
  4. Lukevits, E. Chem. Heter. Comp. 1995, 31, 639-650. https://doi.org/10.1007/BF01169065
  5. Narendar, P.; Parthiban, J.; Anbalagan, N.; Gunasekaran, V.; Leonard, T. J. Biol. Pharm. Bull. 2003, 26, 182-187. https://doi.org/10.1248/bpb.26.182
  6. Bin, H.; Crider, A. M.; Stables, J. P. Eur. J. Med. Chem. 2001, 36, 265-286. https://doi.org/10.1016/S0223-5234(00)01206-X
  7. Kaminski, K.; Obniska, J.; Zagorska, A.; Maciag, D. Arch. Pharm. 2006, 339, 255-261. https://doi.org/10.1002/ardp.200500219
  8. Siddiqui, N.; Alam, P.; Ahsan, W. Arch. Pharm. 2009, 342, 173-181. https://doi.org/10.1002/ardp.200800130
  9. Mamolo, M. G.; Zampieri, D.; Falagiani, V.; Vio, L.; Banfi, E. IL Farmaco 2001, 56, 593-599. https://doi.org/10.1016/S0014-827X(01)01098-9
  10. Krall, R. L.; Penry, J. K.; White, B. G.; Kupferberg, H. J.; Swinyard, E. A. Epilepsia 1978, 19, 409-428. https://doi.org/10.1111/j.1528-1157.1978.tb04507.x
  11. Clark, C. R.; Wells, M. J. M.; Sansom, R. T.; Norris, G. N.; Dockens, R. C.; Ravis, W. R. J. Med. Chem. 1984, 27, 779-782. https://doi.org/10.1021/jm00372a013
  12. Litchfield, J. T.; Wilcoxon, F. J. Pharmacol. Exp. Ther. 1949, 96, 99-113.
  13. Dunham, N. W.; Miya, T. A. J. Am. Pharm. Assoc. Sci. 1957, 46, 208-209.
  14. Reitman, S.; Frankel, S. A. Am. J. Clin. Pathol. 1957, 28, 56-63.
  15. King, E. J.; Armstrong, A. R. Can. Med. Assoc. J. 1934, 31, 376-381.
  16. Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. J. Comput. Chem. 1983, 4, 187-217. https://doi.org/10.1002/jcc.540040211
  17. Eddington, N. D.; Cox, D. S.; Roberts, R. R.; Butcher, R. J.; Edafiogho, I. O.; Stables, J. P.; Cooke, N.; Goodwin, A. M.; Smith, C. A.; Scott, K. R. Eur. J. Med. Chem. 2002, 37, 635-648. https://doi.org/10.1016/S0223-5234(02)01377-6

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