1'-[1-(2-amino-1-benzothiophene-3-carbonyl)piperidin-4-yl]spiro[6,7,8,9-tetrahydro-5H-pyrazolo[1,2-a]diazepine-2,3'-piperidine]-1,3-dione | 1186019-22-6

• 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: 1'-[1-(2-amino-1-benzothiophene-3-carbonyl)piperidin-4-yl]spiro[6,7,8,9-tetrahydro-5H-pyrazolo[1,2-a]diazepine-2,3'-piperidine]-1,3-dione
• CAS: 1186019-22-6
• 化学式: C₂₆H₃₃N₅O₃S
• 分子量: 495.646
• InChiKey: WEFAQPMZLYYQJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1'-[1-(2-amino-1-benzothiophene-3-carbonyl)piperidin-4-yl]spiro[6,7,8,9-tetrahydro-5H-pyrazolo[1,2-a]diazepine-2,3'-piperidine]-1,3-dione 、 异氰酸甲酯 在 吡啶 作用下， 生成 1-[3-[4-(1,3-dioxospiro[6,7,8,9-tetrahydro-5H-pyrazolo[1,2-a]diazepine-2,3'-piperidine]-1'-yl)piperidine-1-carbonyl]-1-benzothiophen-2-yl]-3-methylurea
  参考文献：
  名称：

  Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors

  摘要：

  Spiro-pyrazolidinedione derivatives without quaternary chiral center were discovered by structure-based drug design and characterized as potent acetyl-CoA carboxylase (ACC) inhibitors. The high metabolic stability of the spiro-pyrazolo[1,2-a] pyridazine scaffold and enhancement of the activity by incorporation of a 7-methoxy group on the benzothiophene core successfully led to the identification of compound 4c as an orally bioavailable and highly potent ACC inhibitor. Oral administration of 4c significantly decreased the values of the respiratory quotient in rats, indicating the stimulation of fatty acid oxidation. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.062
• 作为产物：
  描述：

  1-(tert-butoxycarbonyl)-3-(ethoxycarbonyl)piperidine-3-carboxylic acid 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 1'-[1-(2-amino-1-benzothiophene-3-carbonyl)piperidin-4-yl]spiro[6,7,8,9-tetrahydro-5H-pyrazolo[1,2-a]diazepine-2,3'-piperidine]-1,3-dione
  参考文献：
  名称：

  Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors

  摘要：

  Spiro-pyrazolidinedione derivatives without quaternary chiral center were discovered by structure-based drug design and characterized as potent acetyl-CoA carboxylase (ACC) inhibitors. The high metabolic stability of the spiro-pyrazolo[1,2-a] pyridazine scaffold and enhancement of the activity by incorporation of a 7-methoxy group on the benzothiophene core successfully led to the identification of compound 4c as an orally bioavailable and highly potent ACC inhibitor. Oral administration of 4c significantly decreased the values of the respiratory quotient in rats, indicating the stimulation of fatty acid oxidation. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.062