6-benzyloxy-4-formyl-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester | 798564-80-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: 6-benzyloxy-4-formyl-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester
• 英文别名: ethyl 4-formyl-7-methoxy-1-[(3-methoxyphenyl)methyl]-6-phenylmethoxy-1H-isoquinoline-2-carboxylate
• CAS: 798564-80-4
• 化学式: C₂₉H₂₉NO₆
• 分子量: 487.552
• InChiKey: DOXBMZYPRHREQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-benzyloxy-4-formyl-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester 在 甲醇 、 manganese(IV) oxide 、 selenium(IV) oxide 、 palladium on activated charcoal 、 氢气 、 potassium hydroxide 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成
  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
• 作为产物：
  描述：

  (4-benzyloxy-3-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amine 在 盐酸 、 potassium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醚 、 水 、 丙酮 为溶剂， 生成 6-benzyloxy-4-formyl-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester
  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

• 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
• ISOQUINOLINE DERIVATIVES AND THEIR USE AS GFAT INHIBITORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1631551A2

  公开（公告）日：2006-03-08
• US7067529B2
  申请人：——

  公开号：US7067529B2

  公开（公告）日：2006-06-27