8-(2-(benzyloxy)pyridin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane | 1006052-78-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 8-(2-(benzyloxy)pyridin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• 英文别名: 8-(2-(benzyloxy)pyridine-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• CAS: 1006052-78-3
• 化学式: C₁₉H₂₂N₂O₃
• 分子量: 326.395
• InChiKey: FOEXOXSFIGHWGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.0
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  43.82
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  8-(2-(benzyloxy)pyridin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane 在 palladium on activated carbon 盐酸 、 水 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 4.75h， 生成 4-(4-oxopiperidin-1-yl)pyridine-2(1H)-one
  参考文献：
  名称：

  EP2426135

  摘要：

  公开号：
• 作为产物：
  描述：

  2-氯-4-溴吡啶 在 1,3-二甲基-2-咪唑啉酮 、 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.42h， 生成 8-(2-(benzyloxy)pyridin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane
  参考文献：
  名称：

  EP2426135

  摘要：

  公开号：

文献信息

• Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation
  作者：Zhengyu Wang、Xiaofan Shi、Huan Zhang、Liang Yu、Yanhua Cheng、Hefeng Zhang、Huibin Zhang、Jinpei Zhou、Jing Chen、Xu Shen、Wenhu Duan

  DOI：10.1016/j.ejmech.2017.07.051

  日期：2017.10

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.