Nonacidic Chemotype Possessing N-Acylated Piperidine Moiety as Potent Farnesoid X Receptor (FXR) Antagonists,ACS Medicinal Chemistry Letters

当前位置： X-MOL 学术 › ACS Med. Chem. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Nonacidic Chemotype Possessing N-Acylated Piperidine Moiety as Potent Farnesoid X Receptor (FXR) Antagonists
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2018-01-04 00:00:00 , DOI: 10.1021/acsmedchemlett.7b00363
Naoki Teno , Yukiko Yamashita , Yusuke Iguchi , Ko Fujimori ₁ , Mizuho Une , Tomoko Nishimaki-Mogami ₂ , Takie Hiramoto , Keigo Gohda ₃

Affiliation

Farnesoid X receptor (FXR) plays a major role in the control of cholesterol metabolism. Antagonizing transcriptional activity of FXR is an effective means to treat the relevant metabolic syndrome. Some of antagonists so far have the charged functions; however, they may negatively affect the pharmacokinetics. We describe herein a structure–activity relationship (SAR) exploration of nonacidic FXR antagonist 6 focusing on two regions in the structure and biological evaluation of nonacidic 10 with the characteristic N-acylated piperidine group obtained from SAR studies. As the robust affinity to FXR is feasible with our nonacidic analogue, 10 is among the most promising candidates for in vivo testing.

中文翻译：

N-酰基化的哌啶部分具有非酸性化学型，可作为强力法尼醇X受体（FXR）拮抗剂

法尼醇X受体（FXR）在控制胆固醇代谢中起主要作用。拮抗FXR的转录活性是治疗相关代谢综合征的有效手段。到目前为止，一些拮抗剂具有带电功能。但是，它们可能会对药代动力学产生负面影响。我们在此描述了非酸性FXR拮抗剂6的结构-活性关系（SAR）探索，重点研究了非酸性10的结构和生物学评估中的两个区域，这些非酸性FXR拮抗剂具有从SAR研究中获得的具有特征性N-酰化哌啶基团。由于我们的非酸性类似物对FXR具有强大的亲和力，因此10是体内测试中最有希望的候选药物之一。

更新日期：2018-01-04

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11