2. Academic Validation
  3. Discovery of 6-({4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): an orally active antagonist of the gonadotropin releasing hormone receptor (GnRH-R)

Discovery of 6-({4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): an orally active antagonist of the gonadotropin releasing hormone receptor (GnRH-R)

  • J Med Chem. 2009 Apr 9;52(7):2148-52. doi: 10.1021/jm801572m.
Jeffrey C Pelletier 1,  Murty V Chengalvala,  Joshua E Cottom,  Irene B Feingold,  Daniel M Green,  Diane B Hauze,  Christine A Huselton,  James W Jetter,  Gregory S Kopf,  Joseph T Lundquist,  Ronald L Magolda,  Charles W Mann,  John F Mehlmann,  John F Rogers,  Linda K Shanno,  William R Adams,  Cesario O Tio,  Jay E Wrobel
Affiliations

Affiliation

  • 1 Department of Chemical Sciences, Musculoskeletal Biology, and Drug Safety and Metabolism, Wyeth Research, Collegeville, Pennsylvania 19426, USA.
PMID: 19271735 DOI: 10.1021/jm801572m
Abstract

A potent, highly insoluble, GnRH antagonist with a 2-phenyl-4-piperazinylbenzimidazole template and a quinoxaline-2,3-dione pharmacophore was modified to maintain GnRH antagonist activity and improve in vitro pharmaceutical properties. Structural changes to the quinoxaline-2,3-dione portion of the molecule resulted in several structures with improved properties and culminated in the discovery of 6-([4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl] methyl)quinoxaline (WAY-207024). The compound was shown to have excellent pharmacokinetic parameters and lowered rat plasma LH levels after oral administration.

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