4-[4-(methoxymethoxy)phenyl]butan-2-one | 144426-00-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-[4-(methoxymethoxy)phenyl]butan-2-one
• CAS: 144426-00-6
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: AIVBYBDRSPBBOH-UHFFFAOYSA-N

物化性质

• 沸点：
  312.6±27.0 °C(Predicted)
• 密度：
  1.045±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：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[4-(methoxymethoxy)phenyl]butan-2-one 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 3,5-Bis-benzyloxy-4-(2-benzyloxy-6-benzyloxycarbonyl-benzoyl)-benzoic acid 3-(4-methoxymethoxy-phenyl)-1-methyl-propyl ester
  参考文献：
  名称：

  Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A

  摘要：

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

  DOI：

  10.1021/jm960581w
• 作为产物：
  描述：

  氯甲基甲基醚 、 覆盆子酮 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 96.0h， 以70%的产率得到4-[4-(methoxymethoxy)phenyl]butan-2-one
  参考文献：
  名称：

  Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A

  摘要：

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

  DOI：

  10.1021/jm960581w

文献信息

• Interrupting the Barton–McCombie Reaction: Aqueous Deoxygenative Trifluoromethylation of <i>O</i>-Alkyl Thiocarbonates
  作者：Zhi-Yun Liu、Silas P. Cook

  DOI：10.1021/acs.orglett.0c04039

  日期：2021.2.5

  The site-selective trifluoromethylation of aliphatic systems remains an important challenge. This work describes a light-driven, copper-mediated trifluoromethylation of O-alkyl thiocarbonates. The reaction provides broad functional group tolerance (e.g., alkyne, alkene, phenol, free alcohol, electron-rich and -deficient arenes), thereby offering orthogonality and practicality for trifluoromethylation

  脂肪族系统的位点选择性三氟甲基化仍然是一个重要的挑战。这项工作描述了O-烷基硫代碳酸酯的光驱动、铜介导的三氟甲基化。该反应提供了广泛的官能团耐受性（例如，炔烃、烯烃、苯酚、游离醇、富电子和缺电子芳烃），从而为三氟甲基化提供正交性和实用性。提出了一种自由基有机金属机理。
• Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERα
  作者：Kevin D. Dykstra、Liangqin Guo、Elizabeth T. Birzin、Wanda Chan、Yi Tien Yang、Edward C. Hayes、Carolyn A. DaSilva、Lee-Yuh Pai、Ralph T. Mosley、Bryan Kraker、Paula M.D. Fitzgerald、Frank DiNinno、Susan P. Rohrer、James M. Schaeffer、Milton L. Hammond

  DOI：10.1016/j.bmcl.2007.01.054

  日期：2007.4

  A novel class of indole ligands for estrogen receptor alpha have been discovered which exhibit potent affinity and high selectivity. Substitution of the bazedoxifene skeleton to the linker present in the HTS lead 1a provided 22b which was found to be 130-fold alpha-selective and acted as an antagonist of estradiol activity in uterine tissue and MCF-7 cancer cells.
• Screening of σ₂ Receptor Ligands and <i>In Vivo</i> Evaluation of ¹¹C-Labeled 6,7-Dimethoxy-2-[4-(4-methoxyphenyl)butan-2-yl]-1,2,3,4-tetrahydroisoquinoline for Potential Use as a σ₂ Receptor Brain PET Tracer
  作者：Ho Young Kim、Ji Youn Lee、Chia-Ju Hsieh、Aladdin Riad、Nicholas J. Izzo、Susan M. Catalano、Thomas J. A. Graham、Robert H. Mach

  DOI：10.1021/acs.jmedchem.2c00191

  日期：2022.4.28
• DEUBIQUITINASE INHIBITORS AND METHODS FOR USE OF THE SAME
  申请人：The Regents of the University of Michigan

  公开号：EP2619184A2

  公开（公告）日：2013-07-31
• [EN] DEUBIQUITINASE INHIBITORS AND METHODS FOR USE OF THE SAME<br/>[FR] INHIBITEURS DE DÉUBIQUITINASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV MICHIGAN

  公开号：WO2012040527A2

  公开（公告）日：2012-03-29

  Disclosed herein are methods of inhibiting a deubiquitinase (DUB), methods of treating pathogenic infections (e.g., viral, bacterial, and/or parasitic), methods of inhibiting cell proliferation, methods of treating a neurodegenerative disease, methods of treating one or more symptoms of a neurodegenerative disease or a genetic disorder, and compounds.