3-allyloxybenxyl bromide | 69411-94-5

• 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: 3-allyloxybenxyl bromide
• 英文别名: 1-allyloxy-3-bromomethylbenzene；1-Allyloxy-3-bromomethyl-benzene；1-(bromomethyl)-3-prop-2-enoxybenzene
• CAS: 69411-94-5
• 化学式: C₁₀H₁₁BrO
• 分子量: 227.101
• InChiKey: AMSBGWKLDGSPQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-allyloxybenxyl bromide 在 四(三苯基膦)钯 、 正丁基锂 、 碳酸氢钠 、 氯化铵 、 戴斯-马丁氧化剂 、 N-甲基苯胺 、 锌 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.5h， 生成 2-(3-hydroxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)ethan-1-one
  参考文献：
  名称：

  Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy

  摘要：

  Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1 alpha, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1 alpha inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1 alpha inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-la inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1 alpha inhibitors that can be used in lieu of a chromene ring.

  DOI：

  10.1021/acs.jmedchem.8b00971
• 作为产物：
  描述：

  3-羟基苯甲醇 在 三溴化磷 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 15.0h， 生成 3-allyloxybenxyl bromide
  参考文献：
  名称：

  Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy

  摘要：

  Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1 alpha, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1 alpha inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1 alpha inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-la inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1 alpha inhibitors that can be used in lieu of a chromene ring.

  DOI：

  10.1021/acs.jmedchem.8b00971

文献信息

• Carboxamide derivatives as muscarinic receptor antagonists
  申请人：Glossop Alan Paul

  公开号：US20070105831A1

  公开（公告）日：2007-05-10

  The invention relates to compounds of formula processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical composition containing them.

  本发明涉及具有下列公式的化合物、其制备方法和中间体，以及包含它们的抗胆碱能药物组合物。
• Carboxamide Derivatives As Muscarinic Receptor Antagonists
  申请人：Glossop Paul Alan

  公开号：US20100029720A1

  公开（公告）日：2010-02-04

  The invention relates to compounds of formula processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical composition containing them.

  本发明涉及具有以下式的化合物，以及制备它们的过程和中间体，它们作为毒蕈碱受体拮抗剂的用途和包含它们的制药组合物。
• WO2007/34325
  申请人：——

  公开号：——

  公开（公告）日：——
• Inhalation by Design: Novel Tertiary Amine Muscarinic M₃ Receptor Antagonists with Slow Off-Rate Binding Kinetics for Inhaled Once-Daily Treatment of Chronic Obstructive Pulmonary Disease
  作者：Paul A. Glossop、Christine A. L. Watson、David A. Price、Mark E. Bunnage、Donald S. Middleton、Anthony Wood、Kim James、Dannielle Roberts、Ross S. Strang、Michael Yeadon、Christelle Perros-Huguet、Nicholas P. Clarke、Michael A. Trevethick、Ian Machin、Emilio F. Stuart、Steven M. Evans、Anthony C. Harrison、David A. Fairman、Balaji Agoram、Jane L. Burrows、Neil Feeder、Craig K. Fulton、Barry R. Dillon、David A. Entwistle、Fiona J. Spence

  DOI：10.1021/jm200884j

  日期：2011.10.13

  A novel tertiary amine series of potent muscarinic M-3 receptor antagonists are described that exhibit potential as inhaled long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease. Geminal dimethyl functionality present in this series of compounds confers very long dissociative half-life (slow off-rate) from the M-3 receptor that mediates very long-lasting smooth muscle relaxation in guinea pig tracheal strips. Optimization of pharmacokinetic properties was achieved by combining rapid oxidative clearance with targeted introduction of a phenolic moiety to secure rapid glucuronidation. Together, these attributes minimize systemic exposure following inhalation, mitigate potential drug-drug interactions, and reduce systemically mediated adverse events. Compound 47 (PP-3635659) is identified as a Phase II clinical candidate from this series with in vivo duration of action studies confirming its potential for once-daily use in humans.
• Chiral ditopic receptors. Application to palladium-catalyzed allylic alkylation
  作者：Jean Bourguignon、Ulf Bremberg、Georges Dupas、Kristina Hallman、Lars Hagberg、Laurent Hortala、Vincent Levacher、Serghey Lutsenko、Emmanuel Macedo、Christina Moberg、Guy Quéguiner、Fredrik Rahm

  DOI：10.1016/j.tet.2003.10.005

  日期：2003.11

  Chiral pyridinooxazoline, quinolinooxazoline, bis(oxazolino)pyridine (pybox), and bisoxazoline (box) derivatives containing crown ether residues were prepared. Some of the ligands were assessed in substrate binding studies and in palladium catalyzed allylic alkylations. (C) 2003 Elsevier Ltd. All rights reserved.