Bioorganic & Medicinal Chemistry 2008-07-01

2-phenyl-4-piperazinylbenzimidazoles: orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor.

Jeffrey C Pelletier, Murty Chengalvala, Josh Cottom, Irene Feingold, Lloyd Garrick, Daniel Green, Diane Hauze, Christine Huselton, James Jetter, Wenling Kao, Gregory S Kopf, Joseph T Lundquist, Charles Mann, John Mehlmann, John Rogers, Linda Shanno, Jay Wrobel

Index: Bioorg. Med. Chem. 16(13) , 6617-40, (2008)

Full Text: HTML

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.

Related Compounds

  • glycolamide

Related Articles:

Isolation of amidase-negative mutants of Pseudomonas aeruginosa using glycollamide as a selective agent.

1987-06-01

[J. Gen. Microbiol. 133(6) , 1527-33, (1987)]

Extraction capacity of diglycolamide derivatives for Ca(II), Nd(III) and Zr(IV) from nitric acid to N-dodecane containing a solvent modifier.

2005-10-01

[Anal. Sci. 21(10) , 1171-5, (2005)]

Synthesis and evaluation ofin vitroanti-tuberculosis activity ofN-substituted glycolamides

2009-01-01

[Eur. J. Med. Chem. 44(1) , 289-95, (2009)]

Activity profile of glycolamide ester prodrugs of ibuprofen.

2001-01-01

[Drug Dev. Ind. Pharm. 27(1) , 63-70, (2001)]

A QSAR approach for the prediction of stability of benzoglycolamide ester prodrugs.

2006-08-01

[Chem. Pharm. Bull. 54(8) , 1067-71, (2006)]

More Articles...