trans-ethyl 4-((1-(5-(5-chloro-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylate | 1415571-50-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: trans-ethyl 4-((1-(5-(5-chloro-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylate
• CAS: 1415571-50-4
• 化学式: C₂₆H₃₁ClN₄O₃
• 分子量: 483.01
• InChiKey: ABNUQTLAESTCRN-IRJFHVNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.39
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  80.34
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  trans-ethyl 4-((1-(5-(5-chloro-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以59%的产率得到trans-4-((1-(5-(5-chloro-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylic acid
  参考文献：
  名称：

  Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety

  摘要：

  We report the discovery of a novel series of DGAT1 inhibitors in the benzimidazole class with a piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This novel series possesses significantly improved selectivity against the A(2A) receptor, no ACAT1 off-target activity at 10 mu M, and higher aqueous solubility and free fraction in plasma as compared to the previously reported pyridyl-oxy-cyclohexanecarboxylic acid series. In particular, 5B was shown to possess an excellent selectivity profile by screening it against a panel of more than 100 biological targets. Compound 5B significantly reduces lipid excursion in LTT in mouse and rat, demonstrates DGAT1 mediated reduction of food intake and body weight in mice, is negative in a 3-strain Ames test, and appears to distribute preferentially in the liver and the intestine in mice. We believe this lead series possesses significant potential to identify optimized compounds for clinical development.

  DOI：

  10.1021/ml5003426
• 作为产物：
  描述：

  4-羟基吡啶 在 platinum(IV) oxide 、 偶氮二甲酸二异丙酯 、 氢气 、 碳酸氢钠 、 对甲苯磺酸 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 20.0~110.0 ℃ 、310.27 kPa 条件下， 反应 168.0h， 生成 trans-ethyl 4-((1-(5-(5-chloro-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylate
  参考文献：
  名称：

  Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety

  摘要：

  We report the discovery of a novel series of DGAT1 inhibitors in the benzimidazole class with a piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This novel series possesses significantly improved selectivity against the A(2A) receptor, no ACAT1 off-target activity at 10 mu M, and higher aqueous solubility and free fraction in plasma as compared to the previously reported pyridyl-oxy-cyclohexanecarboxylic acid series. In particular, 5B was shown to possess an excellent selectivity profile by screening it against a panel of more than 100 biological targets. Compound 5B significantly reduces lipid excursion in LTT in mouse and rat, demonstrates DGAT1 mediated reduction of food intake and body weight in mice, is negative in a 3-strain Ames test, and appears to distribute preferentially in the liver and the intestine in mice. We believe this lead series possesses significant potential to identify optimized compounds for clinical development.

  DOI：

  10.1021/ml5003426