3-[(1S)-2-(1-acetyl-4-piperidyl)-1-(1-methylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-[(1S)-2-(1-acetyl-4-piperidyl)-1-(1-methylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione
• 英文别名: 3-[(1S)-2-(1-acetylpiperidin-4-yl)-1-(1-methylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione
• 化学式: C₃₂H₃₃N₅O₄
• 分子量: 551.645
• InChiKey: DBZMKOCLVCRXPO-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  88
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-甲基-1,2-苯二胺 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 70.08h， 生成 3-[(1S)-2-(1-acetyl-4-piperidyl)-1-(1-methylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione
  参考文献：
  名称：

  Nonacidic Chemotype Possessing N-Acylated Piperidine Moiety as Potent Farnesoid X Receptor (FXR) Antagonists

  摘要：

  Famesoid 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.

  DOI：

  10.1021/acsmedchemlett.7b00363

文献信息

• Nonacidic Chemotype Possessing <i>N</i>-Acylated Piperidine Moiety as Potent Farnesoid X Receptor (FXR) Antagonists
  作者：Naoki Teno、Yukiko Yamashita、Yusuke Iguchi、Ko Fujimori、Mizuho Une、Tomoko Nishimaki-Mogami、Takie Hiramoto、Keigo Gohda

  DOI：10.1021/acsmedchemlett.7b00363

  日期：2018.2.8

  Famesoid 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.