Tert-butyl 4-[3-cyano-3-(2-methylpropanoylamino)piperidin-1-yl]piperidine-1-carboxylate | 923011-19-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: Tert-butyl 4-[3-cyano-3-(2-methylpropanoylamino)piperidin-1-yl]piperidine-1-carboxylate
• CAS: 923011-19-2
• 化学式: C₂₀H₃₄N₄O₃
• 分子量: 378.515
• InChiKey: QYUYXDFRZIHAHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  85.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[3-cyano-3-(2-methylpropanoylamino)piperidin-1-yl]piperidine-1-carboxylate 在 双氧水 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以55%的产率得到Tert-butyl 4-(4-oxo-2-propan-2-yl-1,3,9-triazaspiro[4.5]dec-1-en-9-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of novel spiro-piperidines as acetyl-CoA carboxylase inhibitors

  摘要：

  Spiro-lactone (S)-1 is a potent acetyl-CoA carboxylase (ACC) inhibitor and was found to be metabolically liable in human hepatic microsomes. To remove one of the risk factors in human study by improving the metabolic stability, we focused on modifying the spiro-lactone ring and the benzothiophene portion of the molecule. Spiro-imide derivative 8c containing a 6-methylthieno[2,3-b]pyridine core exhibited potent ACC inhibitory activity and favorable pharmacokinetic profiles in rats. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.047
• 作为产物：
  描述：

  N-叔丁氧羰基-3-哌啶酮 在 盐酸 、 氨 、 三乙酰氧基硼氢化钠 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 生成 Tert-butyl 4-[3-cyano-3-(2-methylpropanoylamino)piperidin-1-yl]piperidine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of novel spiro-piperidines as acetyl-CoA carboxylase inhibitors

  摘要：

  Spiro-lactone (S)-1 is a potent acetyl-CoA carboxylase (ACC) inhibitor and was found to be metabolically liable in human hepatic microsomes. To remove one of the risk factors in human study by improving the metabolic stability, we focused on modifying the spiro-lactone ring and the benzothiophene portion of the molecule. Spiro-imide derivative 8c containing a 6-methylthieno[2,3-b]pyridine core exhibited potent ACC inhibitory activity and favorable pharmacokinetic profiles in rats. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.047

文献信息

• SPIRO-CYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1911753A1

  公开（公告）日：2008-04-16

  The present invention provides a compound represented by the formula (I): wherein E is an optionally substituted cyclic group; D is a carbonyl group or a sulfonyl group; A is CH or N; ring P is an optionally further substituted 5- to 7-membered ring; ring Q is an optionally further substituted 5- to 7-membered nonaromatic ring; and ring R is an optionally further substituted and optionally condensed 5- to 7-membered nonaromatic ring, or a salt thereof. The compound of the present invention has an ACC inhibitory activity, is useful for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia and the like, and has superior properties in the efficacy, duration of activity, specificity, low toxicity and the like.

  本发明提供了一种由以下式（I）表示的化合物： 其中 E是一个可选择地取代的环状基团； D是一个羰基团或磺酰基团； A是CH或N； 环P是一个可选择进一步取代的5至7元环； 环Q是一个可选择进一步取代的5至7元非芳香环； 环R是一个可选择进一步取代和可选择缩合的5至7元非芳香环，或其盐。本发明的化合物具有ACC抑制活性，对于肥胖、糖尿病、高血压、高脂血症、心力衰竭、糖尿病并发症、代谢综合征、肌肉萎缩等的预防或治疗具有用处，并且在功效、持续活性、特异性、低毒性等方面具有优越性能。
• Design, synthesis, and structure–activity relationships of novel spiro-piperidines as acetyl-CoA carboxylase inhibitors
  作者：Makoto Kamata、Tohru Yamashita、Asato Kina、Masaaki Funata、Atsushi Mizukami、Masako Sasaki、Akiyoshi Tani、Miyuki Funami、Nobuyuki Amano、Kohji Fukatsu

  DOI：10.1016/j.bmcl.2012.04.047

  日期：2012.6

  Spiro-lactone (S)-1 is a potent acetyl-CoA carboxylase (ACC) inhibitor and was found to be metabolically liable in human hepatic microsomes. To remove one of the risk factors in human study by improving the metabolic stability, we focused on modifying the spiro-lactone ring and the benzothiophene portion of the molecule. Spiro-imide derivative 8c containing a 6-methylthieno[2,3-b]pyridine core exhibited potent ACC inhibitory activity and favorable pharmacokinetic profiles in rats. (C) 2012 Elsevier Ltd. All rights reserved.