5-(furan-3-yl)cyclohexane-1,3-dione | 14389-43-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(furan-3-yl)cyclohexane-1,3-dione
• CAS: 14389-43-6
• 化学式: C₁₀H₁₀O₃
• 分子量: 178.188
• InChiKey: NMPOXKDKNJQVPU-UHFFFAOYSA-N

物化性质

• 沸点：
  337.7±42.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-([1,1'-biphenyl]-4-ylmethylene)malononitrile 、 5-(furan-3-yl)cyclohexane-1,3-dione 在 N-甲基吗啉 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以96%的产率得到2-amino-4-([1,1’-biphenyl]-4-yl)-3-cyano-7-(furan-3-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene
  参考文献：
  名称：

  选择性兴奋性氨基酸转运蛋白亚型1（EAAT1）抑制剂UCPH-101和UCPH-102的结构-活性关系的新见解

  摘要：

  在本研究中，我们对选择性兴奋性氨基酸转运蛋白1（EAAT1）抑制剂2-氨基-4-（4-甲氧基苯基）-7-（萘-1-基）-的结构活性要求进行了进一步研究。通过在7位探索15个不同的取代基（R 1）与八个不同的取代基（R）一起合成5-氧代-5,6,7,8-四氢-4 H-色烯3-腈（UCPH-101）2）在4位。在理解了从先前研究中提取的该抑制剂类别的结构-活性关系（SAR）后，我们在合成的63种新类似物中，鉴定出许多化合物在EAAT1上意外表现出抑制活性。此外，R 1和R 2的性质观察到取代基以加和非加方式有助于各种类似物的功能特性。最后，分离出类似物14 g（2-氨基-4-（（[1,1'-联苯] -4-基）-3-氰基-7异丙基-5-氧代-5,6,7）的四种立体异构体（8-四氢-4 H-色烯），并与相关支架的研究相一致，发现C4的R构型对抑制活性是强制性的，而两个C7非对映异构体均具有抑制活性。

  DOI：

  10.1002/cmdc.201500525
• 作为产物：
  描述：

  3-糠醛 在 sodium ethanolate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 36.0h， 生成 5-(furan-3-yl)cyclohexane-1,3-dione
  参考文献：
  名称：

  Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Currently, there is only one FDA-approved treatment for ALS (riluzole), and that drug only extends life, on average, by 2-3 months. Mutations in Cu/Zn superoxide dismutase (SOD1) are found in familial forms of the disease and have played an important role in the study of ALS pathophysiology. On the basis of their activity in a PC12-G93A-YFP high-throughput screening assay, several bioactive compounds have been identified and classified as cyclohexane-1,3-dione (CHD) derivatives. A concise and efficient synthetic route has been developed to provide diverse CHD analogs. The structural modification of the CHD scaffold led to the discovery of a more potent analog (26) with an EC(50) of 700 nM having good pharmacokinetic properties, such as high solubility, low human and mouse metabolic potential, and relatively good plasma stability. It was also found to efficiently penetrate the blood-brain barrier. However, compound 26 did not exhibit any significant life span extension in the ALS mouse model. It was found that, although 26 was active in PC12 cells, it had poor activity in other cell types, including primary cortical neurons, indicating that it can penetrate into the brain, but is not active in neuronal cells, potentially due to poor selective cell penetration. Further structural modification of the CHD scaffold was aimed at improving global cell activity as well as maintaining potency. Two new analogs (71 and 73) were synthesized, which had significantly enhanced cortical neuronal cell permeability, as well as similar potency to that of 26 in the PC12-G93A assay. These CHD analogs are being investigated further as novel therapeutic candidates for ALS. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.039

文献信息

• Cyclohexane-1,3-Diones for Use in the Treatment of Amyotrophic Lateral Sclerosis
  申请人：Kirsch Donald R.

  公开号：US20120264765A1

  公开（公告）日：2012-10-18

  The present invention relates to the identification of provided cyclohexane-1,3-diones (CHD compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided CHD compounds.

  本发明涉及提供的环己烷-1,3-二酮（CHD化合物）的鉴定及其制备的药物组合物，用于治疗患有肌萎缩侧索硬化症（ALS）和其他神经退行性疾病的受试者。本发明还提供了制备所述CHD化合物的方法。
• US8722939B2
  申请人：——

  公开号：US8722939B2

  公开（公告）日：2014-05-13
• US9162968B2
  申请人：——

  公开号：US9162968B2

  公开（公告）日：2015-10-20
• US9593069B2
  申请人：——

  公开号：US9593069B2

  公开（公告）日：2017-03-14
• Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells
  作者：Wei Zhang、Radhia Benmohamed、Anthony C. Arvanites、Richard I. Morimoto、Robert J. Ferrante、Donald R. Kirsch、Richard B. Silverman

  DOI：10.1016/j.bmc.2011.11.039

  日期：2012.1

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Currently, there is only one FDA-approved treatment for ALS (riluzole), and that drug only extends life, on average, by 2-3 months. Mutations in Cu/Zn superoxide dismutase (SOD1) are found in familial forms of the disease and have played an important role in the study of ALS pathophysiology. On the basis of their activity in a PC12-G93A-YFP high-throughput screening assay, several bioactive compounds have been identified and classified as cyclohexane-1,3-dione (CHD) derivatives. A concise and efficient synthetic route has been developed to provide diverse CHD analogs. The structural modification of the CHD scaffold led to the discovery of a more potent analog (26) with an EC(50) of 700 nM having good pharmacokinetic properties, such as high solubility, low human and mouse metabolic potential, and relatively good plasma stability. It was also found to efficiently penetrate the blood-brain barrier. However, compound 26 did not exhibit any significant life span extension in the ALS mouse model. It was found that, although 26 was active in PC12 cells, it had poor activity in other cell types, including primary cortical neurons, indicating that it can penetrate into the brain, but is not active in neuronal cells, potentially due to poor selective cell penetration. Further structural modification of the CHD scaffold was aimed at improving global cell activity as well as maintaining potency. Two new analogs (71 and 73) were synthesized, which had significantly enhanced cortical neuronal cell permeability, as well as similar potency to that of 26 in the PC12-G93A assay. These CHD analogs are being investigated further as novel therapeutic candidates for ALS. (C) 2011 Elsevier Ltd. All rights reserved.