1-(1'-adamantyl)-2-phenyl-1,2-ethanedione | 131273-64-8

• 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: 1-(1'-adamantyl)-2-phenyl-1,2-ethanedione
• 英文别名: 1-((1s,3s)-adamantan-1-yl)-2-phenylethane-1,2-dione；1-(adamantan-1-yl)-2-phenylethane-1,2-dione；1-phenyl-2-tricyclo[3.3.1.1(3,7)]dec-1-ylethane-1,2-dione；1-Adamantan-1-yl-2-phenylethane-1,2-dione；1-(1-adamantyl)-2-phenylethane-1,2-dione
• CAS: 131273-64-8
• 化学式: C₁₈H₂₀O₂
• 分子量: 268.356
• InChiKey: MVEIEEZWAKLYGG-UHFFFAOYSA-N

物化性质

• 熔点：
  76-77 °C
• 沸点：
  388.9±11.0 °C(Predicted)
• 密度：
  1.193±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  1-(1'-adamantyl)-2-phenyl-1,2-ethanedione 在 caesium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.25h， 生成 tert-butyl (4-(4-(adamantan-1-yl)-2-(methylthio)-5-oxo-4-phenyl-4,5-dihydro-1H-imidazol-1-yl)butan-2-yl)carbamate
  参考文献：
  名称：

  Allosteric Modulation of Protein Arginine Methyltransferase 5 (PRMT5)

  摘要：

  Protein arginine methyltransferase 5 (PRMT5) belongs to a family of enzymes that regulate the posttranslational modification of histones and other proteins via methylation of arginine. Methylation of histones is linked to an increase in transcription and regulates a manifold of functions such as signal transduction and transcriptional regulation. PRMT5 has been shown to be upregulated in the tumor environment of several cancer types, and the inhibition of PRMT5 activity was identified as a potential way to reduce tumor growth. Previously, four different modes of PRMT5 inhibition were known-competing (covalently or non-covalently) with the essential cofactor Sadenosyl methionine (SAM), blocking the substrate binding pocket, or blocking both simultaneously. Herein we describe an unprecedented conformation of PRMT5 in which the formation of an allosteric binding pocket abrogates the enzyme's canonical binding site and present the discovery of potent small molecule allosteric PRMT5 inhibitors.

  DOI：

  10.1021/acsmedchemlett.9b00525
• 作为产物：
  描述：

  苯甲醛 在 lithium diisopropyl amide 作用下， 反应 8.0h， 生成 1-(1'-adamantyl)-2-phenyl-1,2-ethanedione
  参考文献：
  名称：

  Synthetic methods and reactions. 159. Preparation of 1,2-diketones from nonenolizable aliphatic and aromatic acyl chlorides with diethyl 1-alkyl(aryl)-1-(trimethylsiloxy)-methanephosphonates

  摘要：

  DOI：

  10.1021/jo00002a085

文献信息

• Cycloalkyl amino-hydantoin compounds and use thereof for beta-secretase modulation
  申请人：Malamas Sotirios Michael

  公开号：US20070027199A1

  公开（公告）日：2007-02-01

  The present invention provides a 2-amino-5-cycloalkyl-hydantoin compound of formula I The present invention also provides methods and compositions for the inhibition of β-secretase (BACE) and the treatment of β-amyloid deposits and neurofibrillary tangles.

  本发明提供了一种公式I的2-氨基-5-环烷基乙内酰脲化合物。 本发明还提供了一种用于抑制β-分泌酶（BACE）以及治疗β-淀粉样蛋白沉积和神经纤维缠结的方法和组合物。
• Dimethyl Sulfoxide as an Oxygen Atom Source Enabled Tandem Conversion of 2‐Alkynyl Carbonyls to 1,2‐Dicarbonyls
  作者：Yuan Lu、Mu‐Jia Luo、Ming Hu、Yang Li、Jin‐Heng Li

  DOI：10.1002/adsc.202000066

  日期：2020.4.27

  compounds by means of a CuBr2/I2/DMSO/water system is developed, enabling the fromation of various functionalized 1,2‐dicarbonyl compounds, including 1,2‐diketones, α‐keto amides and α‐keto ester. This Cu‐promoted iodine‐mediated tandem procedure employs DMSO as the oxygen atom source of the formed carbonyl group through iodonium ion formation, nucleophilic DMSO addition and C−C bond cleavage cascades.

  开发了通过CuBr 2 / I 2 / DMSO /水系统串联2-炔基羰基化合物的方法，使各种官能化的1,2-二羰基化合物（包括1,2-二酮，α-酮酰胺）形成和α-酮酸酯 此铜促进的碘介导的串联过程使用DMSO作为碘原子离子形成，亲核DMSO加成和CC键断裂级联反应形成的羰基的氧原子源。
• Design and Synthesis of 5,5′-Disubstituted Aminohydantoins as Potent and Selective Human β-Secretase (BACE1) Inhibitors
  作者：Michael S. Malamas、Jim Erdei、Iwan Gunawan、Jim Turner、Yun Hu、Erik Wagner、Kristi Fan、Rajiv Chopra、Andrea Olland、Jonathan Bard、Steve Jacobsen、Ronald L. Magolda、Menelas Pangalos、Albert J. Robichaud

  DOI：10.1021/jm901414e

  日期：2010.2.11

  The identification of small molecule aminohydantoins as potent and selective human β-secretase inhibitors is reported. These analogues exhibit low nannomolar potency for BACE1, show comparable activity in a cell-based (ELISA) assay, and demonstrate >100× selectivity for the other structurally related aspartyl proteases BACE2, cathepsinD, renin, and pepsin. On the basis of the cocrystal structure of

  报道了鉴定小分子氨基乙内酰脲作为有效的和选择性的人β-分泌酶抑制剂。这些类似物对BACE1表现出低的纳米摩尔效价，在基于细胞的（ELISA）分析中显示出可比的活性，并且对其他结构相关的天冬氨酰蛋白酶BACE2，组织蛋白酶D，肾素和胃蛋白酶显示出大于100倍的选择性。基于BACE1活性位点中HTS-hit 2的共晶体结构，并使用基于结构的药物设计方法，我们系统地探索了BACE1酶的较大结合口袋，并确定了配体与有助于亲和力的蛋白质。一种更有效的化合物（S）-55的IC 50的BACE1值为10 nM，在ELISA分析中显示出可比的细胞活性（EC 50 = 20 nM）。急性口服100 mg / kg的（S）-55导致Tg2576小鼠在8 h时血浆Aβ40降低69％（p <0.001）。
• CYCLOALKYL AMINO-HYDANTOIN COMPOUNDS AND USE THEREOF FOR ß-SECRETASE MODULATION
  申请人：Wyeth

  公开号：EP1910309A2

  公开（公告）日：2008-04-16
• [EN] CYCLOALKYL AMINO-HYDANTOIN COMPOUNDS AND USE THEREOF FOR ß-SECRETASE MODULATION<br/>[FR] COMPOSES DE CYCLOALKYL AMINO-HYDANTOIN ET LEUR UTILISATION POUR MODULER LA $G(B)-SECRETASE
  申请人：WYETH CORP

  公开号：WO2007016012A2

  公开（公告）日：2007-02-08

  [EN] The present invention provides a 2-amino-5-cycloalkyl-hydantoin compound of formula (I) The present invention also provides methods and compositions for the inhibition of ß-secretase (BACE) and the treatment of ß-amyloid deposits and neurofibrillary tangles.
  [FR] L'invention concerne un composé de 2-amino-5-cycloalkyl-hydantoin représenté par la formule (I). L'invention concerne également des méthodes et des compositions permettant d'inhiber la ß-secrétase (BACE) et de traiter les dépôts ß-amyloïdes et les enchevêtrements neurofibrillaires.