1-[Hydroxy-(3-methoxyphenyl)methyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid | 1344688-62-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-[Hydroxy-(3-methoxyphenyl)methyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid
• CAS: 1344688-62-5
• 化学式: C₂₀H₁₉NO₆
• 分子量: 369.374
• InChiKey: SQULJGIXJCYPFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氨基-2-(3,4-二甲氧基苯基)丙酸乙酯 在 五氯化磷 、 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 sulfur 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 1-[Hydroxy-(3-methoxyphenyl)methyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid
  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

• 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.