Author/Authors :
Jeffrey C. Pelletier، نويسنده , , Murty Chengalvala، نويسنده , , Josh Cottom، نويسنده , , Irene Feingold، نويسنده , , Lloyd Garrick، نويسنده , , Daniel Green، نويسنده , , Diane Hauze، نويسنده , , Christine Huselton، نويسنده , , James Jetter، نويسنده , , Wenling Kao، نويسنده , , Gregory S. Kopf، نويسنده , , Joseph T. Lundquist IV، نويسنده , , Charles Mann، نويسنده , , John Mehlmann، نويسنده , , John Rogers، نويسنده , , Linda Shanno، نويسنده , , Jay Wrobel، نويسنده ,
Abstract :
Antagonism of the gonadotropin releasing hormone (GnRH) receptor has shown positive clinical results in numerous reproductive tissue disorders such as endometriosis, prostate cancer and others. Traditional therapy has been limited to peptide agonists and antagonists. Recently, small molecule GnRH antagonists have emerged as potentially new treatments. This article describes the discovery of 2-phenyl-4-piperazinylbenzimidazoles as small molecule GnRH antagonists with nanomolar potency in in vitro binding and functional assays, excellent bioavailability (rat %F > 70) and demonstrated oral activity in a rat model having shown significant serum leuteinizing hormone (LH) suppression.
Keywords :
Small molecule , oral activity , Gonadotropin releasing hormone antagonist , Pharmaceutical profiling
