2. Academic Validation
  3. Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen receptor modulator

Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen receptor modulator

  • J Med Chem. 2012 Oct 11;55(19):8236-47. doi: 10.1021/jm300281x.
François Nique 1,  Séverine Hebbe,  Nicolas Triballeau,  Christophe Peixoto,  Jean-Michel Lefrançois,  Hélène Jary,  Luke Alvey,  Murielle Manioc,  Christopher Housseman,  Hugo Klaassen,  Kris Van Beeck,  Denis Guédin,  Florence Namour,  Dominque Minet,  Ellen Van der Aar,  Jean Feyen,  Stephen Fletcher,  Roland Blanqué,  Catherine Robin-Jagerschmidt,  Pierre Deprez
Affiliations

Affiliation

  • 1 GALAPAGOS, Parc Biocitech, 102 Avenue Gaston Roussel, 93230 Romainville, France.
PMID: 22957947 DOI: 10.1021/jm300281x
Abstract

Structural modification performed on a 4-methyl-4-(4-hydroxyphenyl)hydantoin series is described which resulted in the development of a new series of 4-(hydroxymethyl)diarylhydantoin analogues as potent, partial agonists of 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) evaluated in vivo in a classical model of orchidectomized rat. In this model, (-)-18a exhibited anabolic activity on muscle, strongly dissociated from the androgenic activity on prostate after oral dosing. (-)-18a has very good pharmacokinetic properties, including bioavailability in rat (F > 50%), and is currently under evaluation in phase I clinical trials.

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