Discovery of a Novel, Orally Active, Small Molecule Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist
- 26 April 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (11) , 3362-3367
- https://doi.org/10.1021/jm060012g
Abstract
Gonadotropin releasing hormone (GnRH) plays an important role in the biology of reproduction. The use of GnRH receptor antagonists has been reported in the literature for the treatment of breast, ovarian, and prostate cancers. In this article, we report the synthesis, in vitro characterization, pharmacokinetics, and pharmacodynamics of an orally bioavailable, potent, small molecule GnRH receptor antagonist N-{4,6-dimethoxy-2-[(3-morpholin-4-ylpropyl)amino]pyrimidin-5-yl}-5-[3,3,6-trimthyl-2,3-dihydro-1H-inden-5-yl)oxy]-2-furamide (compound 1).Keywords
This publication has 15 references indexed in Scilit:
- New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonistsExpert Opinion on Investigational Drugs, 2005
- Synthesis and Structure–activity relationships of 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils as antagonists of the human GnRH ReceptorBioorganic & Medicinal Chemistry Letters, 2003
- Biological Characterization of a Novel, Orally Active Small Molecule Gonadotropin-Releasing Hormone (GnRH) Antagonist Using Castrated and Intact RatsThe Journal of Pharmacology and Experimental Therapeutics, 2003
- A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonistsBioorganic & Medicinal Chemistry Letters, 2002
- Synthesis and initial structure–Activity relationships of a novel series of imidazolo[1,2-a]pyrimid-5-ones as potent GnRH receptor antagonistsBioorganic & Medicinal Chemistry Letters, 2002
- Effect of testosterone suppression on the pharmacokinetics of a potent gnRH receptor antagonist.Pharmaceutical Research, 2002
- Treatment of Localized Prostate Cancer With Intermittent Triple Androgen Blockade: Preliminary Results in 110 Consecutive PatientsThe Oncologist, 2001
- Hormonal treatment for prostate cancerExpert Opinion on Investigational Drugs, 2001
- Pharmacological and endocrine characterization of A-198401, an orally active GnRH antagonist, in intact and castrate male rat modelsDrug Development Research, 2001
- Daily Rhythmicity of Serum Testosterone Concentration in the Male Laboratory Rat*Endocrinology, 1978