Synthesis of androgen receptor antagonists containing a pentafluorosulfanyl (SF5 ) moiety

Arch Pharm (Weinheim). 2018 Nov;351(11):e1800175. doi: 10.1002/ardp.201800175. Epub 2018 Oct 15.

Abstract

A novel scaffold of pentafluorosulfanyl (SF5 )-containing enzalutamide analogues was discovered for potent androgen receptor (AR) antagonists through rational drug design. Several compounds showed good biological profiles in AR binding. Of the derivatives studied, compound 8a had potent AR antagonist activity (IC50 = 7.1 ± 1.0 µM) and high efficacy (104.5 ± 12.8%). It exhibited an inhibitory effect comparable to that of enzalutamide (inhibition = 66.0 and 77.9%, respectively) in a prostate cancer cell line. The results point to the potential of using this scaffold to develop new AR antagonists.

Keywords: androgen receptor; antagonist; enzalutamide; pentafluorosulfanyl.

MeSH terms

  • Androgen Receptor Antagonists / chemical synthesis
  • Androgen Receptor Antagonists / chemistry
  • Androgen Receptor Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Fluorides / chemical synthesis
  • Fluorides / chemistry
  • Fluorides / pharmacology*
  • Humans
  • Molecular Structure
  • Receptors, Androgen / metabolism*
  • Structure-Activity Relationship
  • Sulfur Compounds / chemical synthesis
  • Sulfur Compounds / chemistry
  • Sulfur Compounds / pharmacology*

Substances

  • Androgen Receptor Antagonists
  • Receptors, Androgen
  • Sulfur Compounds
  • sulfur pentafluoride cation
  • Fluorides