5-benzylcyclohexane-1,3-dione | 40398-05-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-benzylcyclohexane-1,3-dione
• 英文别名: 5-benzyl-cyclohexane-1,3-dione；5-Benzyl-cyclohexan-1,3-dion
• CAS: 40398-05-8
• 化学式: C₁₃H₁₄O₂
• 分子量: 202.253
• InChiKey: WYHYLVFEMYKTNG-UHFFFAOYSA-N

物化性质

• 熔点：
  118 °C
• 沸点：
  360.7±25.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-benzylcyclohexane-1,3-dione 在 正丁基锂 、 三氟化硼 、 溴 、 三乙胺 、 三苯基膦 作用下， 生成
  参考文献：
  名称：

  立体选择性合成四环素抗生素的方法

  摘要：

  如通过单晶X射线结构测定所证实的那样，使官能化的β-乙烯基乙酰基阴离子当量与苯并环丁二酮单缩醛反应，然后添加甲基锂，产生具有精制成四环素所必需的立体化学的三环结构。

  DOI：

  10.1039/c39860000828
• 作为产物：
  描述：

  4-苯基-3-丁烯酸 在 乙醇 、 硫酸 、 sodium aceto-acetate 作用下， 生成 5-benzylcyclohexane-1,3-dione
  参考文献：
  名称：

  Linstead; Williams, Journal of the Chemical Society, 1926, p. 2745

  摘要：

  DOI：

文献信息

• Structure−Activity Relationship Study of First Selective Inhibitor of Excitatory Amino Acid Transporter Subtype 1: 2-Amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4<i>H</i>-chromene-3-carbonitrile (UCPH-101)
  作者：Mette N. Erichsen、Tri H. V. Huynh、Bjarke Abrahamsen、Jesper F. Bastlund、Christoffer Bundgaard、Olja Monrad、Anders Bekker-Jensen、Christina W. Nielsen、Karla Frydenvang、Anders A. Jensen、Lennart Bunch

  DOI：10.1021/jm1009154

  日期：2010.10.14

  The excitatory amino acid transporters (EAATs) are expressed throughout the central nervous system, where they are responsible for the reuptake of the excitatory neurotransmitter (S)-glutamate (Glu).(1) Recently, we have reported the discovery of the first subtype selective EAAT1 inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101)

  兴奋性氨基酸转运蛋白（EAAT）在整个中枢神经系统中表达，它们负责兴奋性神经递质（S）-谷氨酸（Glu）的再摄取。（1）最近，我们报道了第一个亚型的发现。选择性EAAT1抑制剂2-氨基-4-（4-甲氧基苯基）-7-（萘-1-基）-5-氧代-5,6,7,8-四氢-4 H-亚甲基-3-腈（UCPH- 101）（1b）并进行了结构-活性关系（SAR）的入门研究。（2）在这里，我们通过类似物1g - 1t的设计，合成和药理学评估给出了详细的SAR 。通过比较1b，1h和1i的效能与1j相比，很明显，效力很大程度上受R 1取代基的化学性质影响。该研究还表明，官能团的任何化学变化或亲本支架的变化都会导致化合物在EAAT1处的抑制活性完全丧失。最终，UCPH-101的生物利用度研究确定其在血清（大鼠）中的半衰期为30分钟，但它也无法显着穿透血脑屏障。
• [EN] ALDOSTERONE SYNTHASE INHIBITORS<br/>[FR] INHIBITEURS DE L'ALDOSTÉRONE SYNTHASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2016123275A1

  公开（公告）日：2016-08-04

  The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, wherein X, R1, R2 and R3 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及公式I的化合物及其药学上可接受的盐，其中X、R1、R2和R3的定义如本文所述。该发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和障碍的方法，制备这些化合物的过程以及在这些过程中有用的中间体。
• 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。
• Aldosterone synthase inhibitors
  申请人：Boehringer Ingelheim International GmbH

  公开号：US10131642B1

  公开（公告）日：2018-11-20

  The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, wherein X, R1, R2 and R3 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式 I 的化合物：及其药学上可接受的盐类，其中 X、R1、R2 和 R3 如本文所定义。本发明还涉及包含这些化合物的药物组合物、使用这些化合物治疗各种疾病和失调的方法、制备这些化合物的工艺以及在这些工艺中有用的中间体。
• 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.