nbi-42902 and elagolix

nbi-42902 has been researched along with elagolix* in 2 studies

Other Studies

2 other study(ies) available for nbi-42902 and elagolix

Article	Year
Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist. Journal of medicinal chemistry, 2016, 10-13, Volume: 59, Issue:19 We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clinically advanced compound. Considering that 18a exhibited highly potent and selective antagonistic activity toward the hGnRHRs along with favorable pharmacokinetic profiles, we believe that 18a may represent a promising candidate for an orally available hormonal therapy. Topics: Adamantane; Administration, Oral; Animals; Biological Availability; Dogs; Drug Discovery; Humans; Hydrocarbons, Fluorinated; Macaca fascicularis; Male; Pyrimidines; Rats; Rats, Sprague-Dawley; Receptors, LHRH	2016
Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human Journal of medicinal chemistry, 2008, Dec-11, Volume: 51, Issue:23 The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis. Topics: Animals; Caco-2 Cells; Cytochrome P-450 CYP3A Inhibitors; Drug Discovery; Drug Evaluation, Preclinical; Humans; Hydrocarbons, Fluorinated; Macaca fascicularis; Male; Microsomes, Liver; Molecular Structure; Pyrimidines; Receptors, LHRH; Stereoisomerism; Structure-Activity Relationship; Time Factors	2008

Article

Year

Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist.

Journal of medicinal chemistry, 2016, 10-13, Volume: 59, Issue:19

We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clinically advanced compound. Considering that 18a exhibited highly potent and selective antagonistic activity toward the hGnRHRs along with favorable pharmacokinetic profiles, we believe that 18a may represent a promising candidate for an orally available hormonal therapy.

Topics: Adamantane; Administration, Oral; Animals; Biological Availability; Dogs; Drug Discovery; Humans; Hydrocarbons, Fluorinated; Macaca fascicularis; Male; Pyrimidines; Rats; Rats, Sprague-Dawley; Receptors, LHRH

2016

Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human

Journal of medicinal chemistry, 2008, Dec-11, Volume: 51, Issue:23

The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis.

Topics: Animals; Caco-2 Cells; Cytochrome P-450 CYP3A Inhibitors; Drug Discovery; Drug Evaluation, Preclinical; Humans; Hydrocarbons, Fluorinated; Macaca fascicularis; Male; Microsomes, Liver; Molecular Structure; Pyrimidines; Receptors, LHRH; Stereoisomerism; Structure-Activity Relationship; Time Factors

2008