Journal of medicinal chemistry

other 2008

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 gonadotropin-releasing hormone receptor

doi:10.1021/jm8006454 ·PMID:19006286

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 liabi…

2006

Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.

doi:10.1021/jm060240a ·PMID:16759096

Novel degarelix (Fe200486) analogues were screened for antagonism of GnRH-induced response (IC(50)) in a reporter gene assay. Inhibition of luteinizing hormone release over time was measured in the castrated male rat. N(omega)-Hydroxy- and …

2005

Iterative approach to the discovery of novel degarelix analogues: substitutions at positions 3, 7, and 8. Part II.

doi:10.1021/jm050134t ·PMID:16033265

Degarelix (FE200486, Ac-d-2Nal(1)-d-4Cpa(2)-d-3Pal(3)-Ser(4)-4Aph(l-Hor)(5)-d-4Aph(Cbm)(6)-Leu(7)-ILys(8)-Pro(9)-d-Ala(10)-NH(2)) is a potent and very long acting antagonist of gonadotropin-releasing hormone (GnRH) after subcutaneous admini…

other 2005

Synthesis and discovery of pyrazine-pyridine biheteroaryl as a novel series of potent vascular endothelial growth factor receptor-2 inhibitors

doi:10.1021/jm040099a ·PMID:15771433

Pathological angiogenesis is associated with disease states such as cancer, diabetic retinopathy, rheumatoid arthritis, endometriosis, and psoriasis. There is much evidence that direct inhibition of the kinase activity of vascular endotheli…

other 2000

Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist

doi:10.1021/jm001000c ·PMID:11150172

Herein we describe the chemical synthesis and pharmacological characterization of a novel, highly potent progesterone receptor (PR) antagonist, ZK 230211. The introduction of a 17alpha-pentafluorethyl side chain in the D-ring of the steroid…