959694-01-0Relevant articles and documents
Discovery of diarylhydantoins as new selective androgen receptor modulators
Nique, Francois,Hebbe, Severine,Peixoto, Christophe,Annoot, Denis,Lefrancois, Jean-Michel,Duval, Eric,Michoux, Laurence,Triballeau, Nicolas,Lemoullec, Jean-Michel,Mollat, Patrick,Minet, Dominique,Clement-Lacroix, Philippe,Robin-Jagerschmidt, Catherine,Fleury, Damien,Guedin, Denis,Deprez, Pierre,Thauvin, Maxime,Prange, Thierry
, p. 8225 - 8235,11 (2020/09/15)
A novel selective androgen receptor modulator scaffold has been discovered through structural modifications of hydantoin antiandrogens. Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayed partial agonism with nanomolar in vitro potency in transactivation experiments using androgen receptor (AR) transfected cells. In a standard castrated male rat model, several compounds showed good anabolic activity on levator ani muscle, dissociated from the androgenic activity on ventral prostate, after oral dosing at 30 mg/kg. (+)-4-[3,4-Dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl] -2-(trifluoromethyl)benzonitrile ((+)-11b) displayed anabolic potency with a strong dissociation between levator ani muscle and ventral prostate (A 50 = 0.5 mg/kg vs 70 mg/kg). The binding modes of two compounds, including (+)-11b, within the AR ligand-binding domain have been studied by cocrystallization experiments using a coactivator-like peptide. Both compounds bound to the same site, and the overall structures of the AR were very similar.
Imidazolidine Derivatives, Uses Therefor, Preparation Thereof and Compositions Comprising Such
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Page/Page column 23, (2010/04/23)
Compounds of formula (I): wherein X is O or S, R1 is acyl, aldehyde, cycloalkyl, an optionally substituted alkyl, alkenyl or alkynyl, R2 is H. alkyl, hydroxyalkyl, haloalkyl, alkenyl, or alkynyl; substituted alkyl; alkylcarbonyl; R3 and R4 are H, halogen, alkyl, alkenyl, alkynyl, alkoxyl, alkylthio, hydroxyalkyl, haloalkyl, haloalkenyl, or haloalkynyl; or R3 and R4 form an, optionally aromatic or heterocyclic, optionally substituted ring, R5 is H, halogen, trifluoromethyl, —CN, or —NO2; not all of R3, R4, and R5 being H, R6 and R9 are H, halogen, OH; alkyl. hydroxyalkyl, alkoxyl, thioalkyl, haloalkyl, alkenyl, or alkynyl; R7 and R8 are H, halogen, OH, SH; alkoxyl or alkylthio optionally substituted by OH and/or halogen; one of R7 and R8 not being H or halogen; or one of R7 and R8 is a pharmaceutically acceptable ester or thioester grouping, or R6 is C1-3-alkyl or, together with either R1 or R2, represents C1-3 alkylene or alkenylene linking group, optionally substituted by methyl, trifluoromethyl, OH, or halogen, and pharmaceutically acceptable salts and esters thereof, are useful as selective androgen modulators.
