6,7-Dimethoxy-1-[(3-methoxyphenyl)carbamoyl]isoquinoline-4-carboxylic acid | 1344688-61-4

• 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: 6,7-Dimethoxy-1-[(3-methoxyphenyl)carbamoyl]isoquinoline-4-carboxylic acid
• CAS: 1344688-61-4
• 化学式: C₂₀H₁₈N₂O₆
• 分子量: 382.373
• InChiKey: IOHDJKVEEXVKED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  107
• 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 selenium(IV) oxide 、 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 、 乙酸乙酯 为溶剂， 生成 6,7-Dimethoxy-1-[(3-methoxyphenyl)carbamoyl]isoquinoline-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