4.7 Article

Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist

期刊

JOURNAL OF MEDICINAL CHEMISTRY
卷 59, 期 19, 页码 9150-9172

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01071

关键词

-

资金

  1. Korea Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI11C0918]

向作者/读者索取更多资源

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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据