학술논문
Identification of a 4-(Hydroxymethyl)diarylhydantoinas a Selective Androgen Receptor Modulator.
Document Type
Article
Author
Nique, François; Hebbe, Séverine; Triballeau, Nicolas; Peixoto, Christophe; Lefrançois, Jean-Michel; Jary, Hélène; Alvey, Luke; Manioc, Murielle; Housseman, Christopher; Klaassen, Hugo; Van Beeck, Kris; Guédin, Denis; Namour, Florence; Minet, Dominque; Van der Aar, Ellen; Feyen, Jean; Fletcher, Stephen; Blanqué, Roland; Robin-Jagerschmidt, Catherine; Deprez, Pierre
Source
Subject
*HYDROXYMETHYL compounds
*ANDROGEN receptors
*IMIDAZOLIDINES
*LABORATORY rats
*PHARMACOKINETICS
*BIOAVAILABILITY
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Language
ISSN
0022-2623
Abstract
Structural modification performed on a 4-methyl-4-(4-hydroxyphenyl)hydantoinseries is described which resulted in the development of a new seriesof 4-(hydroxymethyl)diarylhydantoin analogues as potent, partial agonistsof the human androgen receptor. This led to the identification of(S)-(−)-4-(4-(hydroxymethyl)-3-methyl-2,5-dioxo-4-phenylimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile((S)-(−)-18a, GLPG0492) evaluatedin vivo in a classical model of orchidectomized rat. In this model,(−)-18aexhibited anabolic activity on muscle,strongly dissociated from the androgenic activity on prostate afteroral dosing. (−)-18ahas very good pharmacokineticproperties, including bioavailability in rat (F>50%), and is currently under evaluation in phase I clinical trials. [ABSTRACT FROM AUTHOR]