Synthesis and structure-activity studies of side-chain derivatized arylhydantoins for investigation as androgen receptor radioligands

Bioorg Med Chem Lett. 2001 Apr 23;11(8):1045-7. doi: 10.1016/s0960-894x(01)00146-9.

Abstract

A series of arylhydantoin derivatives modeled after the antiandrogen RU 58841 was generated to identify potential candidates for development as androgen receptor (AR) radioligands. Side-chain modified derivatives of RU 58841, suitable for labeling with either carbon-11 or radiohalogens (fluorine-18, iodine-123), were synthesized and tested for their AR binding affinities. The N-(iodopropenyl) derivative 13 (Ki = 13 nM) is a potential candidate for development as a radioiodinated AR ligand.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgen Antagonists / chemical synthesis*
  • Androgen Antagonists / metabolism
  • Androgen Antagonists / pharmacology*
  • Animals
  • Binding Sites / physiology
  • Carbon Isotopes / chemistry
  • Fluorine / chemistry
  • Hydantoins / chemical synthesis
  • Hydantoins / metabolism
  • Imidazoles / chemical synthesis*
  • Imidazoles / metabolism
  • Imidazoles / pharmacology*
  • Nitriles / chemical synthesis*
  • Nitriles / metabolism
  • Nitriles / pharmacology*
  • Radioligand Assay
  • Rats
  • Receptors, Androgen / metabolism*
  • Structure-Activity Relationship

Substances

  • 4-(4,4-dimethyl-2,5-dioxo-3-N-(iodopropenyl)-1-imidazolidinyl)-2- (trifluoromethyl)benzonitrile
  • Androgen Antagonists
  • Carbon Isotopes
  • Hydantoins
  • Imidazoles
  • Nitriles
  • Receptors, Androgen
  • RU 58841
  • Fluorine