Design and synthesis of novel androgen receptor antagonists with sterically bulky icosahedral carboranes

Bioorg Med Chem. 2005 Dec 1;13(23):6414-24. doi: 10.1016/j.bmc.2005.06.061. Epub 2005 Aug 15.

Abstract

Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable chemical and thermal stability, and hydrophobic character. These features may allow application of carboranes as a new hydrophobic core structure in biologically active molecules that interact hydrophobically with receptors. Here, we report the design and synthesis of novel androgen antagonists bearing a carborane moiety. These compounds, particularly 8a, 8c, and 9d, exhibited anti-androgenic activity similar to that of the well-known anti-androgen flutamide in reporter gene assay using NIH3T3 cells transfected with a human AR expression plasmid. The carborane cage seems to be a privileged hydrophobic pharmacophore for the expression of AR-antagonistic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / chemical synthesis*
  • Androgen Antagonists / chemistry
  • Androgen Antagonists / pharmacology*
  • Androgen Receptor Antagonists*
  • Animals
  • Dihydrotestosterone / metabolism
  • Drug Design*
  • Mice
  • Molecular Structure
  • NIH 3T3 Cells
  • Receptors, Androgen / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Androgen Antagonists
  • Androgen Receptor Antagonists
  • Receptors, Androgen
  • Dihydrotestosterone