5-(3,5-bis(trifluoromethyl)phenyl)cyclohexane-1,3-dione | 1307260-51-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(3,5-bis(trifluoromethyl)phenyl)cyclohexane-1,3-dione
• 英文别名: 5-[3,5-Bis(trifluoromethyl)phenyl]cyclohexane-1,3-dione
• CAS: 1307260-51-0
• 化学式: C₁₄H₁₀F₆O₂
• 分子量: 324.223
• InChiKey: NUQVZPNQASEHFH-UHFFFAOYSA-N

物化性质

• 沸点：
  312.9±42.0 °C(Predicted)
• 密度：
  1.405±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 4-phenyl-2-oxo-3-butenoate 、 5-(3,5-bis(trifluoromethyl)phenyl)cyclohexane-1,3-dione 在 3-{[(S)-{5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl}(6-methoxyquinolin-4-yl)methyl]amino}-4-[(2-fluorophenyl)amino]cyclobut-3-ene-1,2-dione 、 ammonium acetate 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 50.75h， 以50%的产率得到methyl (4R,7R)‐7‐(3,5-bis(trifluoromethyl)phenyl)‐5‐oxo‐4‐phenyl‐1,4,5,6,7,8‐hexahydroquinoline‐2‐carboxylate
  参考文献：
  名称：

  Cinchona Squaramide催化的1,3-二酮的分子间脱对称导致手性1,4-二氢吡啶

  摘要：

  在使用双官能金鸡纳衍生的方酰胺的迈克尔受体上添加前手性环状1,3-二酮会导致手性加合物的立体选择性高达99％ee，并允许亲核试剂脱对称。这些不稳定的半缩醛中间体被转化为新的1,4-二氢吡啶，具有高非对映选择性，且不会破坏光学纯度。它们进一步氧化为吡啶，然后进行费舍尔吲哚化，提供了手性吡啶吲哚。

  DOI：

  10.1002/adsc.202000455
• 作为产物：
  描述：

  3,5-双三氟甲基苯甲醛 在 sodium ethanolate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 36.0h， 生成 5-(3,5-bis(trifluoromethyl)phenyl)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
• [EN] CYCLOHEXANE-1,3-DIONES FOR USE IN THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS<br/>[FR] CYCLOHEXANE-1,3-DIONES POUR EMPLOI DANS LE TRAITEMENT DE LA SCLÉROSE LATÉRALE AMYOTROPHIQUE
  申请人：CAMBRIA PHARMACEUTICALS INC

  公开号：WO2011059821A2

  公开（公告）日：2011-05-19

  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.