Synthesis and Antiinflammatory Activity of 1,5-Diarylimidazoles

  • Published : 2005.09.01

Abstract

A number of 1,5-diarylimidazoles has been synthesized and evaluated for their inhibitory activities of COX-2 catalyzed $PGE_2$ production. 1,5-Diarylimidazoles were obtained from imimes and p-toluenesulfonylmethyl cyanide (TosMIC). Imines were prepared from commercially available amines and aldehydes. Among the compounds tested, 1-(2,4-difluorophenyl)-5-(4­methylsulfonylphenyl)imidazole (2r) showed strong inhibitory activity, however, most diarylimidazoles exhibited little to low inhibitory activities against COX-2 catalyzed $PGE_2$ production.

Keywords

References

  1. Albert, M. V. L., Jurjen, W., and Otto, H. O., Based-induced cycloaddition of sulfonylmethyl isocyanides to C,N double bonds. Synthesis of 1,5-disubstituted and 1,4,5-trisubstituted imidazoles from aldimines and imidoyl chlorides. J. Org. Chem., 42, 1153-1159 (1977) https://doi.org/10.1021/jo00427a012
  2. Almansa, C., Alfon, J., de Arriba, A. F., Cavalcanti, F. L., Escamilla, I., Gomez, L. A, Miralles, A, Soliva, R, Bartroli, J., Carceller, E., Merlos, M., and Garcia-Rafanell, J., Synthesis and structure-activity relationship of a new series of COX-2 selective inhibitors: 1,5-diarylimidazoles. J. Med. Chem., 46, 3463-3475 (2003) https://doi.org/10.1021/jm030765s
  3. Askin, D., Cowen, J. A, Maligres, P. E., McWilliams, J. C., and Waters, M. S., Process for making 1,5-disubstituted Imidazoles, US Patent 6,140,508 (2000)
  4. Barta, T. E., Stealey, M. A., Collins, P. W., and Weier, R. M., Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors. Bioorg. Med. Chem. Lett., 8, 3443-3448 (1998) https://doi.org/10.1016/S0960-894X(98)00627-1
  5. Black, W. C., Selective cyclooxygenase-2 inhibitors. Ann. Rep. Med. Chem., 39,125-138 (2004) https://doi.org/10.1016/S0065-7743(04)39010-X
  6. Chi, Y. S., Cheon, B. S., and Kim, H. P., Effect of Wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lopopolysaccharide-treated RAW 264.7 cells. Biochem. Pharmacol., 61, 1195-1203 (2001) https://doi.org/10.1016/S0006-2952(01)00597-4
  7. John, B., and Jerome, S., Synthesis of Oxazolyl- and Furanylsubstituted Imidazole Hydrochlorides and Methiodides. J. Heterocyclic Chem., 35, 859-863 (1998) https://doi.org/10.1002/jhet.5570350413
  8. Kuwano, E., Takeya, R., Eto, M., and Asano, S., 1,5- disubstituted imidazoles as inhibitors of Juvenile hormone. US Patent 4,812,473 (1989)
  9. Needleman, P. and Isakson, P., The discovery and function of COX-2. J. Rhematol. 24(Suppl. 49), 6-8 (1997)
  10. Stanley, R. S. and Wolf, K., Organic functional group preparations, Academic Press, INC., Florida, pp. 291-322, (1986)