Non-steroidal glucocorticoid-like substances: receptor binding and in vivo activity

J Med Chem. 1993 Oct 29;36(22):3278-85. doi: 10.1021/jm00074a008.

Abstract

Compounds of general structure I, prepared by a Diels-Alder reaction with diene 3, are relatives of the known potent glucocorticoid II but possess a markedly modified C- and D-ring environment. Despite these structural changes, 4, 5, 9, 10, 12a, 13, and 14 bound to the glucocorticoid receptor with an affinity which approximated that of the reference standard, 6-alpha-methylprednisolone. Four of these compounds not only exhibited antiinflammatory activity in the alpha-tocopherol pouch test but also exhibited marked adrenal suppression and other typical glucocorticoid properties at doses in the same range as the effective antiinflammatory doses.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Glucocorticoids / chemical synthesis*
  • Glucocorticoids / metabolism
  • Glucocorticoids / pharmacology*
  • Male
  • Pyrazoles / chemical synthesis
  • Pyrazoles / metabolism
  • Pyrazoles / pharmacology
  • Rats
  • Receptors, Glucocorticoid / metabolism*
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Glucocorticoids
  • Pyrazoles
  • Receptors, Glucocorticoid