Jeffrey C Pelletier, 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
Department of Chemical Sciences, Musculoskeletal Biology, and Drug Safety and Metabolism, Wyeth Research, Collegeville, Pennsylvania 19426, USA.
Journal of medicinal chemistry 2009 Apr 9A 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.
Jeffrey C Pelletier, 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. 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). Journal of medicinal chemistry. 2009 Apr 9;52(7):2148-52
PMID: 19271735
View Full Text