1308375-93-0Relevant articles and documents
Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist
Kim, Seon-Mi,Lee, Minhee,Lee, So Young,Park, Euisun,Lee, Soo-Min,Kim, Eun Jeong,Han, Min Young,Yoo, Taekyung,Ann, Jihyae,Yoon, Suyoung,Lee, Jiyoun,Lee, Jeewoo
, p. 9150 - 9172 (2016/10/22)
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.
GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, MANUFACTURING METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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Page/Page column 21; 22, (2011/12/12)
Disclosed are compounds useful as gonadotropin-releasing hormone ("GnRH") receptor antagonist.