Synthesis and structure-activity investigation of iodinated arylhydantoins and arylthiohydantoins for development as androgen receptor radioligands

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5285-8. doi: 10.1016/j.bmcl.2004.08.031.


A series of side-chain derivatives of the arylhydantoin RU 58841 and the arylthiohydantoin RU 59063, wherein the aromatic trifluoromethyl group was replaced with iodine, was synthesized for possible development as radioiodinated androgen receptor (AR) ligands. Derivatives containing the cyanomethyl, methoxyethyl and propenyl side-chains displayed moderately high affinity (K(i)=20-59nM) towards the rat AR. Side-chains containing bulky lipophilic groups such as, benzyl and phenylpropyl, were poorly tolerated (K(i)>219nM). Superior AR binding affinities (0.71nM<K(i)<11nM) were displayed by arylhydantoins and arylthiohydantoin derivatives containing hydroxybutyl or methyl side-chains. The latter compounds are potential candidates for development as radioiodinated AR ligands.

Publication types

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

MeSH terms

  • Animals
  • Binding, Competitive
  • Hydantoins / chemical synthesis*
  • Hydantoins / pharmacology
  • Imidazoles / chemical synthesis
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Ligands
  • Male
  • Nitriles / chemical synthesis
  • Nitriles / pharmacology
  • Prostate / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Androgen / metabolism*
  • Structure-Activity Relationship


  • Hydantoins
  • Imidazoles
  • Iodine Radioisotopes
  • Ligands
  • Nitriles
  • Receptors, Androgen
  • RU 58841
  • RU 59063