6-Hydroxy-7-methoxy-1-(3-methoxybenzoyl)isoquinoline-4-carboxylic acid | 1344688-59-0

• 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: 6-Hydroxy-7-methoxy-1-(3-methoxybenzoyl)isoquinoline-4-carboxylic acid
• 英文别名: 6-hydroxy-7-methoxy-1-(3-methoxybenzoyl)isoquinoline-4-carboxylic acid
• CAS: 1344688-59-0
• 化学式: C₁₉H₁₅NO₆
• 分子量: 353.331
• InChiKey: OAWODOMRPJFXHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  [1-(4-benzyloxy-3-methoxy-phenyl)-2-(3-methoxy-phenyl)-ethyl]-(2,2-dimethoxy-ethyl)-carbamic acid ethyl ester 在 盐酸 、 甲醇 、 manganese(IV) oxide 、 selenium(IV) oxide 、 disodium hydrogenphosphate 、 2-甲基-2-丁烯 、 palladium on activated charcoal 、 氢气 、 potassium hydroxide 、 三氯氧磷 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 丙酮 、 叔丁醇 为溶剂， 生成 6-Hydroxy-7-methoxy-1-(3-methoxybenzoyl)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

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.