Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and Characterization of Novel Hydantoins as Potential COX-2 Inhibitors: 1,5-Diarylhydantoins

  • Published : 2007.05.20
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Abstract

To develop new COX-2 inhibitors, 1,5-diarylhydantoins and 1,5-diaryl-2-thiohydantoins were synthesized from phenylacetic acids by esterification, bromination, C-N bond formation and cyclization. Esters 1-3 were efficiently synthesized from the starting materials by reflux in absolute methanol for 3 h containing concentrated sulfuric acid as catalyst. Bromination was carried out with N-bromosuccinimide at rt in dichloromethane. Bromides 4-6 were reacted with aniline, p-anisidine, sulfanilamide in ethanol (or N,N-dimethylformamide) to provide the amines 7-15. Hydantoins and 2-thiohydantoins 16-46 were synthesized from amines 7-15 by treating them with potassium isocyanate (or potassium thiocyanate) and triethylamine. The synthetic process from alkyl α-anilinophenylacetate 7-15 to 3-alkylhydantoins was carried out in a one-pot reaction using alkyl isocyanate (alkyl isothiocyanate).

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References

  1. Hardman, J. G.; Limbird, L. E. In Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed.; McGraw-Hill: New York, 2001; pp 688-731
  2. Lombardino, G. Nonsteroidal Antiinflammtory Drugs; John Wiely & Sons: New York, 1985. 2. Allison, M. C.; Howatson, A. G.; Torrance, C. J.; Lee, F. D.; Russell, R. I. G. N. Engl. J. Med. 1992, 327, 749 https://doi.org/10.1056/NEJM199209103271101
  3. Fu, J. Y.; Masfferrer, J. L.; Seibert, K.; Raz, A.; Needleman, P. J. Biol. Chem. 1990, 265, 16737
  4. Vane, J.; Botting, J.; Botting, R. Improved Non-steroid Anti-inflammatory Drugs COX-2 Enzyme Inhibitors; Kluwer Academic Publishers and William Harvey Press: London, 1996
  5. Hla, T.; Neilson, K. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7384 https://doi.org/10.1073/pnas.89.16.7384
  6. Xie, W.; Chipman, J. G.; Robertson, D. L.; Erikson, R. L.; Simmons, D. L. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 2692 https://doi.org/10.1073/pnas.88.7.2692
  7. Kujubu, D. A.; Fletcher, B. S.; Varnum, B. C.; Lim, R. W.; Herschman, H. R. J. Biol. Chem. 1991, 266, 12866
  8. Masferrer, J. L.; Seibert, K.; Zweifel, B.; Needleman, P. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 3917 https://doi.org/10.1073/pnas.89.9.3917
  9. Futaki, N.; Yoshikawa, K.; Hamasaka, Y.; Arai, I.; Higuchi, S.; Iizuka, H.; Otomo, S. Gen. Pharmacol. 1993, 24, 105 https://doi.org/10.1016/0306-3623(93)90018-S
  10. Futaki, N.; Takahashi, S.; Yokoyama, M.; Arai, I.; Higuchi, S.; Otomo, S. Prostaglandins 1994, 47, 55 https://doi.org/10.1016/0090-6980(94)90074-4
  11. Gans, K. R.; Galnraith, W.; Romans, R. J.; Haber, S. B.; Kerr, J. S.; Schmidt, W. K.; Smith, C.; Hewes, W. E.; Ackerman, N. R. J. Pharmacol. Exp. Ther. 1990, 254, 180
  12. Penning, T. D.; Tally, J. J.; Bertenshaw, S. R.; Carter, J. S.; Collins, P. W.; Doctor, S.; Graneto, M. J.; Lee, L. F.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson, P. C. J. Med. Chem. 1997, 40, 1347 https://doi.org/10.1021/jm960803q
  13. Prasit, P.; Wang, Z.; Brideau, C.; Chan, C.-C.; Charleson, S.; Cromlish, W.; Ethier, D.; Evans, J. F.; Ford-Hutchinson, A. W.; Gauthier, J. Y.; Gordon, R.; Forrest, M.; Visco, D.; Patrick, D. Bioorg. Med. Chem. Lett. 1999, 9, 1773
  14. Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Rogers, R. S.; Shaffer, A. F.; Zhang, Y. Y.; Zweifel, B. S.; Seibert, K. J. Med. Chem. 2000, 43, 775 https://doi.org/10.1021/jm990577v
  15. Kwon, S. K.; Jung, H. W.; Park, M. S. Korean J. Med. Chem. 1995, 5, 166
  16. Wolfe, M. M.; Lichtenstein, D. R.; Singh, G. N. Engl. J. Med. 1999, 340, 1888 https://doi.org/10.1056/NEJM199906173402407
  17. Mukherjee, D.; Nissen, S. E.; Topol, E. J. JAMA 2001, 286, 954 https://doi.org/10.1001/jama.286.8.954
  18. Gaetano, G.; Donati, M. B.; Cerletti, C. Trends Pharm. Sci. 2003, 24, 245 https://doi.org/10.1016/S0165-6147(03)00077-4
  19. Hwang, K. J.; Lee, S. J.; Kim, B. T.; Raucher, S. Bull. Korean Chem. Soc. 2006, 27(6), 933 https://doi.org/10.5012/bkcs.2006.27.6.933
  20. Park, M. S.; Park, H. S. Yakhak Hoeji 2003, 47, 276
  21. Kirk-Othmer Encyclopedia of Chemical Technology, 2nd ed.; Interscience: New York-London-Sydney, 1966; Vol 11, pp 141- 161
  22. Ware, E. Chem. Rev. 1950, 411
  23. Li, J. P. Org. Chem. 1975, 40, 3414 https://doi.org/10.1021/jo00911a024
  24. Kirk-Othmer Encyclopedia of Chemical Technology, 3nd ed.; Interscience: New York-London Sydney, 1979; Vol 12, pp 692-708

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