2-(3,4-dimethoxyphenyl)-3-{{[(3,4-dimethoxyphenyl)methyl]carbonyl}amino}propanoic acid ethyl ester | 95520-62-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(3,4-dimethoxyphenyl)-3-{{[(3,4-dimethoxyphenyl)methyl]carbonyl}amino}propanoic acid ethyl ester
• 英文别名: ethyl 2-(3,4-dimethoxyphenyl)-3-[[2-(3,4-dimethoxyphenyl)acetyl]amino]propanoate
• CAS: 95520-62-0
• 化学式: C₂₃H₂₉NO₇
• 分子量: 431.486
• InChiKey: JPENUHIEKZCDIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-3-{{[(3,4-dimethoxyphenyl)methyl]carbonyl}amino}propanoic acid ethyl ester 在 五氯化磷 作用下， 以 二氯甲烷 为溶剂， 生成 Ethyl 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline-4-carboxylate
  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：

  3,4-二甲氧基苯乙腈 在 盐酸 、 palladium on activated charcoal 、 氢气 、 sodium 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 80.0 ℃ 、344.75 kPa 条件下， 生成 2-(3,4-dimethoxyphenyl)-3-{{[(3,4-dimethoxyphenyl)methyl]carbonyl}amino}propanoic 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

• Substituted isoquinolines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04544657A1

  公开（公告）日：1985-10-01

  Substituted isoquinolines of the formula ##STR1## wherein R is lower alkoxy, n is the integer zero or 1, and A is ##STR2## wherein R.sub.1 is phenyl, halophenyl, lower-alkylphenyl or lower-alkoxyphenyl, and pharmaceutically acceptable acid addition salts thereof, are described. The compounds of formula I are useful in the treatment of cerebral and cardiac ischemias.

  描述了公式为##STR1##的替代异喹啉，其中R为较低的烷氧基，n为整数0或1，A为##STR2##，其中R.sub.1为苯基，卤苯基，较低烷基苯基或较低烷氧基苯基，以及其药学上可接受的酸盐。公式I的化合物在治疗脑和心脏缺血中很有用。
• BRUDERER, H.;KIERSTEAD, R. W.;MULLIN, J. G. ,, JR.;NAKAMURA, KEIJI;TATEIS+
  作者：BRUDERER, H.、KIERSTEAD, R. W.、MULLIN, J. G. ,, JR.、NAKAMURA, KEIJI、TATEIS+

  DOI：——

  日期：——
• US4544657A
  申请人：——

  公开号：US4544657A

  公开（公告）日：1985-10-01
• US4559403A
  申请人：——

  公开号：US4559403A

  公开（公告）日：1985-12-17
• 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.