diethyl (acetylamino)<3-(2-hydroxy-5-methylphenyl)-3-oxopropyl>propanedioate | 220542-05-2

• 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: diethyl (acetylamino)<3-(2-hydroxy-5-methylphenyl)-3-oxopropyl>propanedioate
• 英文别名: Diethyl (acetylamino)[3-(2-hydroxy-5-methylphenyl)-3-oxopropyl]propanedioate；diethyl 2-acetamido-2-[3-(2-hydroxy-5-methylphenyl)-3-oxopropyl]propanedioate
• CAS: 220542-05-2
• 化学式: C₁₉H₂₅NO₇
• 分子量: 379.41
• InChiKey: SMTVQCCDYRSNJG-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：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl (acetylamino)<3-(2-hydroxy-5-methylphenyl)-3-oxopropyl>propanedioate 在 盐酸 作用下， 反应 15.0h， 以100%的产率得到5-(2-Hydroxy-5-methyl-phenyl)-3,4-dihydro-2H-pyrrole-2-carboxylic acid; hydrochloride
  参考文献：
  名称：

  Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators

  摘要：

  Further structure-activity studies of desferrithiocin analogues are carried out. (S)-desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous imp act on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2,4-dihydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.

  DOI：

  10.1021/jm980340j
• 作为产物：
  描述：

  (4-甲基苯基)3-氯丙酸酯 在 三氯化铝 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 19.15h， 生成 diethyl (acetylamino)<3-(2-hydroxy-5-methylphenyl)-3-oxopropyl>propanedioate
  参考文献：
  名称：

  Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators

  摘要：

  Further structure-activity studies of desferrithiocin analogues are carried out. (S)-desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous imp act on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2,4-dihydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.

  DOI：

  10.1021/jm980340j

文献信息

• Method and composition for treatment of inflammatory bowel disease
  申请人：——

  公开号：US20030211978A1

  公开（公告）日：2003-11-13

  A composition in unit dosage form for the inhibition, prevention or treatment of inflammatory bowel disease comprising an effective amount of a compound having the formula: 1 and a pharmaceutically acceptable carrier therefor. Also disclosed is a method for the inhibition, prevention or treatment of inflammatory bowel disease comprising administering to a human or non-human mammal in need thereof an effective amount of a compound having the formula: 2

  一种单元剂量形式的组合物，用于抑制、预防或治疗炎症性肠病，包括具有以下式子的化合物的有效量：1，并含有药学上可接受的载体。本发明还公开了一种用于抑制、预防或治疗炎症性肠病的方法，包括向需要的人类或非人类哺乳动物施用具有以下式子的化合物的有效量：2
• Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators
  作者：Raymond J. Bergeron、Jan Wiegand、William R. Weimar、J. R. Timothy Vinson、Jörg Bussenius、Guo Wei Yao、James S. McManis

  DOI：10.1021/jm980340j

  日期：1999.1.1

  Further structure-activity studies of desferrithiocin analogues are carried out. (S)-desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous imp act on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2,4-dihydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.