(4-benzyloxy-3-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amine | 74199-70-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4-benzyloxy-3-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amine
• 英文别名: N-(2,2-dimethoxyethyl)-1-(3-methoxy-4-phenylmethoxyphenyl)methanimine
• CAS: 74199-70-5
• 化学式: C₁₉H₂₃NO₄
• 分子量: 329.396
• InChiKey: LSUFRFNPQFTHPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-benzyloxy-3-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amine 在 palladium 10% on activated carbon 盐酸 、 manganese(IV) oxide 、 氢氧化钾 、 氢气 、 碘 、 potassium carbonate 、 magnesium 、 三氯氧磷 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 DMF (N,N-dimethyl-formamide) 、 乙醚 、 乙醇 、 氯仿 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 85.0 ℃ 、101.33 kPa 条件下， 反应 86.08h， 生成 6-(3-bromo-propoxy)-7-methoxy-1-(3-ethoxy-benzyl)-isoquinoline-4-carbaldehyde
  参考文献：
  名称：

  [EN] ISOQUINOLINE DERIVATIVES AND THEIR USE AS GFAT INHIBITORS
  [FR] INHIBITEURS DE LA GFAT

  摘要：

  公开号：

  WO2004101528A3
• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲醛 、 氨基乙醛缩二甲醇 在 原甲酸三甲酯 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 (4-benzyloxy-3-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amine
  参考文献：
  名称：

  Discovery of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitors

  摘要：

  Through high throughput screening and subsequent hit identification and optimization, we synthesized a series of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as the first reported potent and reversible GFAT inhibitors. SAR studies of this class of compounds indicated significant impact on GFAT inhibition potency by substitutions on the A-ring and C-ring. The ketone group was found to be necessary for high potency. Compound 28 (RO0509347) demonstrated potent GFAT inhibition (IC(50) = 1 mu M) with a desirable pharmacokinetic profile in rats, and showed significant efficacy in reducing the glucose excursion in an OGTT test in ob/ob mice. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.009

文献信息

• Chimeric microtubule disruptors
  作者：Mathew P. Leese、Fabrice Jourdan、Meriel R. Kimberley、Gyles E. Cozier、Nethaji Thiyagarajan、Chloe Stengel、Sandra Regis-Lydi、Paul A. Foster、Simon P. Newman、K. Ravi Acharya、Eric Ferrandis、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1039/c002558e

  日期：——

  A chimeric approach is used to discover microtubule disruptors with excellent in vitro activity and oral bioavailability; a ligand-protein interaction with carbonic anhydrase that enhances bioavailability is characterised by protein X-ray crystallography. Dosing of a representative chimera in a tumour xenograft model confirms the excellent therapeutic potential of the class.

  嵌合方法用于发现具有出色的体外活性和口服生物利用度的微管破坏物。蛋白质X射线晶体学表征了与碳酸酐酶的配体-蛋白质相互作用，该相互作用增强了生物利用度。肿瘤异种移植模型中典型嵌合体的给药证实了该类药物的极好的治疗潜力。
• Glutamine fructose-y-phosphate amidotransferase (GFAT) inhibitors
  申请人：——

  公开号：US20040259910A1

  公开（公告）日：2004-12-23

  Compounds of formula I are provided 1 as well as pharmaceutically acceptable salts and esters thereof, wherein the substituents are as disclosed in the specification. The compounds have utility for the treatment of type 2 diabetes mellitus.

  提供了化学式I的化合物，以及其药学上可接受的盐和酯，其中取代基如规范中所披露。这些化合物可用于治疗2型糖尿病。
• [EN] ISOQUINOLINE DERIVATIVES AND THEIR USE AS GFAT INHIBITORS<br/>[FR] INHIBITEURS DE LA GFAT
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004101528A3

  公开（公告）日：2005-01-06
• Discovery of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitors
  作者：Yimin Qian、Mushtaq Ahmad、Shaoqing Chen、Paul Gillespie、Nam Le、Frank Mennona、Steven Mischke、Sung-Sau So、Hong Wang、Charles Burghardt、Shahid Tannu、Karin Conde-Knape、Jarema Kochan、David Bolin

  DOI：10.1016/j.bmcl.2011.09.009

  日期：2011.11

  Through high throughput screening and subsequent hit identification and optimization, we synthesized a series of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as the first reported potent and reversible GFAT inhibitors. SAR studies of this class of compounds indicated significant impact on GFAT inhibition potency by substitutions on the A-ring and C-ring. The ketone group was found to be necessary for high potency. Compound 28 (RO0509347) demonstrated potent GFAT inhibition (IC(50) = 1 mu M) with a desirable pharmacokinetic profile in rats, and showed significant efficacy in reducing the glucose excursion in an OGTT test in ob/ob mice. (C) 2011 Elsevier Ltd. All rights reserved.