5-(naphthalen-2-yl)cyclohexane-1,3-dione | 1247933-05-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-(naphthalen-2-yl)cyclohexane-1,3-dione
• 英文别名: 5-(naphtalen-2-yl)cyclohexane-1,3-dione；5-Naphthalen-2-ylcyclohexane-1,3-dione
• CAS: 1247933-05-6
• 化学式: C₁₆H₁₄O₂
• mdl: MFCD23091665
• 分子量: 238.286
• InChiKey: BQKLSCZUTXHPJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 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-(naphthalen-2-yl)cyclohexane-1,3-dione 、 methyl 4-phenyl-2-oxo-3-butenoate 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‐(naphtalen-2-yl)‐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：

  在 硫酸 作用下， 反应 4.5h， 以4.07 g的产率得到5-(naphthalen-2-yl)cyclohexane-1,3-dione
  参考文献：
  名称：

  兴奋性氨基酸转运蛋白亚型1的第一种选择性抑制剂的构效关系研究：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-苯甲基-3-腈（UCPH-101）

  摘要：

  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。

  DOI：

  10.1021/jm1009154

文献信息

• 一种异色烯类化合物及其制备方法和用途
  申请人：西华大学

  公开号：CN113135884B

  公开（公告）日：2023-03-10

  本发明提供了一种异色烯类化合物及其制备方法和用途。本发明公开了一种异色烯类化合物，所述异色烯类化合物的结构如式A所示，该化合物具有良好的生物活性，能够有效抑制SIRT1和SIRT5的活性，在制备治疗和/或预防代谢性疾病、肿瘤或神经退行性疾病的药物中具有良好的应用前景。本发明还提供了该化合物的制备方法，所述制备方法无需催化剂，具有反应条件温和、操作便捷、收率高、产物易纯化等优点。
• Pd/C-Catalyzed Carbonylative Amidation for the Synthesis of 2-Carboxamidocyclohexane-1,3-diones
  作者：Sheetal、Arvind Singh Chauhan、Ajay Kumar Sharma、Navneet Sharma、Kousik Giri、Pralay Das

  DOI：10.1021/acs.orglett.3c02808

  日期：2023.11.24

  first-ever heterogeneous Pd/C-catalyzed single-step tandem approach for the synthesis of 2-carboxamidocyclohexane-1,3-diones via direct carbonylative C–H amidation of cyclohexane-1,3-diones is reported. The reaction progressed under base-, oxidant-, and ligand-free conditions employing oxalic acid as a CO surrogate and sodium azide as a nitrogen precursor in a double-layer vial system.

  在此，报道了有史以来第一个非均相 Pd/C 催化的单步串联方法，通过环己烷-1,3-二酮的直接羰基化 C-H 酰胺化合成 2-甲酰胺基环己烷-1,3-二酮。该反应在双层小瓶系统中，在无碱、无氧化剂和无配体的条件下进行，使用草酸作为CO替代物，叠氮化钠作为氮前体。
• Copper-catalyzed one-pot [3 + 2] cycloadditions of ethynyl indoloxazolidones with 1,3-cyclohexanediones
  作者：Qing-Qiang Su、Ruo-Nan Wang、Yong-Zheng Lv、Ya-Xin Fan、Shan Li、Hong-Li Huang、Ji-Yuan Du

  DOI：10.1039/d3ob00332a

  日期：——

  units in natural products and medicinal molecules, and methods for their introduction are of fundamental importance. Here we report one-pot cycloadditions of ethynyl indoloxazolidones with 1,3-cyclohexanediones enabled by copper catalysis, leading to a series of functionalized furan derivatives in good yields. This method features mild reaction conditions, high efficiency, and wide substrate scope

  稠合呋喃是天然产物和药用分子中常见的单元，引入它们的方法至关重要。在这里，我们报告了通过铜催化实现的乙炔基吲哚恶唑烷酮与 1,3-环己二酮的一锅法环加成，从而以良好的收率生成了一系列功能化的呋喃衍生物。该方法反应条件温和、效率高、底物适用范围广。
• 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.
• 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。