具有酰化哌啶部分的非酸性化学型作为强效法尼醇X受体（FXR）拮抗剂。
Nonacidic Chemotype Possessing -Acylated Piperidine Moiety as Potent Farnesoid X Receptor (FXR) Antagonists.
作者信息
Teno Naoki, Yamashita Yukiko, Iguchi Yusuke, Fujimori Ko, Une Mizuho, Nishimaki-Mogami Tomoko, Hiramoto Takie, Gohda Keigo
机构信息
Graduate School of Pharmaceutical Sciences, Faculty of Clinical Nutrition, and Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan.
Faculty of Pharmaceutical Sciences, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
出版信息
ACS Med Chem Lett. 2018 Jan 4;9(2):78-83. doi: 10.1021/acsmedchemlett.7b00363. eCollection 2018 Feb 8.
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 focusing on two regions in the structure and biological evaluation of nonacidic with the characteristic -acylated piperidine group obtained from SAR studies. As the robust affinity to FXR is feasible with our nonacidic analogue, is among the most promising candidates for testing.
法尼醇X受体（FXR）在胆固醇代谢控制中起主要作用。拮抗FXR的转录活性是治疗相关代谢综合征的有效手段。迄今为止，一些拮抗剂具有带电功能；然而，它们可能会对药代动力学产生负面影响。我们在此描述了一种非酸性FXR拮抗剂的构效关系（SAR）探索，重点关注结构中的两个区域，并对通过SAR研究获得的具有特征性酰化哌啶基团的非酸性化合物进行了生物学评估。由于我们的非酸性类似物对FXR具有强大的亲和力，因此它是最有希望进行测试的候选物之一。
Zotero 插件