Synthesis and structure-activity studies of side-chain derivatized arylhydantoins for investigation as androgen receptor radioligands.
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.
Van Dort
M E
ME
Department of Radiology, The University of Michigan Medical School, Ann Arhor 48109-0552, USA. mvandort@umich.edu
Jung
Y W
YW
D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002247:Carbon Isotopes / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D006827:Hydantoins / Q000138:chemical synthesis / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D009570:Nitriles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D013329:Structure-Activity Relationship
C434824:4-(4,4-dimethyl-2,5-dioxo-3-N-(iodopropenyl)-1-imidazolidinyl)-2- (trifluoromethyl)benzonitrile; D000726:Androgen Antagonists; D002247:Carbon Isotopes; D006827:Hydantoins; D007093:Imidazoles; D009570:Nitriles; D011944:Receptors, Androgen; C086458:RU 58841; D005461:Fluorine