Novel non-steroidal/non-anilide type androgen antagonists with an isoxazolone moiety

Bioorg Med Chem. 2002 May;10(5):1555-66. doi: 10.1016/s0968-0896(01)00421-7.

Abstract

3-Substituted (Z)-4-(4-N,N-dialkylaminophenylmethylene)-5(4H)-isoxazolones and related compounds were designed and prepared as candidates for structurally novel androgen antagonists. Several compounds showed potent anti-androgenic activity as assessed by nuclear androgen receptor binding assay and growth inhibition assay using androgen-dependent Shionogi carcinoma cells SC-3. They were approximately 10--220 times more potent than flutamide in these assay systems. They also showed anti-androgenic activity toward prostate tumor cell line LNCaP, which has an aberrant nuclear androgen receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / chemical synthesis*
  • Androgen Antagonists / pharmacology
  • Cell Division / drug effects
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Isoxazoles / chemical synthesis
  • Isoxazoles / pharmacology*
  • Protein Binding / drug effects
  • Receptors, Androgen / metabolism
  • Structure-Activity Relationship
  • Testosterone / metabolism
  • Testosterone / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Androgen Antagonists
  • Isoxazoles
  • Receptors, Androgen
  • Testosterone