ethyl (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl)-4-methyl-4-thiazolecarboxylate | 1221411-72-8

• 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: ethyl (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl)-4-methyl-4-thiazolecarboxylate
• 英文别名: (S)-Ethyl 2-(2-hydroxy-4-(2-(2-methoxyethoxy)ethoxy)phenyl)-4-methyl-4,5-dihydrothiazole-4-carboxylate；ethyl (4S)-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-5H-1,3-thiazole-4-carboxylate
• CAS: 1221411-72-8
• 化学式: C₁₈H₂₅NO₆S
• 分子量: 383.466
• InChiKey: CWSQBHXIYLLJCI-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl)-4-methyl-4-thiazolecarboxylate 在 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 78.0h， 生成 isopropyl (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl)-4-methyl-4-thiazolecarboxylate
  参考文献：
  名称：

  [EN] DESFERRITHIOCIN POLYETHER ANALOGUES AND USES THEREOF
  [FR] ANALOGUES DE POLYÉTHER DESFERRITHIOCINE ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2011028255A3
• 作为产物：
  描述：

  ethyl (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate 、 2-(2-甲氧基乙氧基)乙基4-甲基苯磺酸负离子 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 48.0h， 以73%的产率得到ethyl (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl)-4-methyl-4-thiazolecarboxylate
  参考文献：
  名称：

  The Impact of Polyether Chain Length on the Iron Clearing Efficiency and Physiochemical Properties of Desferrithiocin Analogues

  摘要：

  (S)-2-(2,4-Dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid (2) was abandoned in clinical trials as an iron chelator for the treatment of iron overload disease because of its nephrotoxicity. However, subsequent investigations revealed that replacing the 4'-(HO) of 2 with a 3,6,9-trioxadecyloxy group, ligand 4, increased iron clearing efficiency (ICE) and ameliorated the renal toxicity of 2. This compelled a closer look at additional polyether analogues, the subject of this work. The 3,6,9,12-tetraoxatridecyloxy analogue of 4, chelator 5, an oil, had twice the ICE in rodents of 4, although its ICE in primates was reduced relative to 4. The corresponding 3,6-dioxaheptyloxy analogue of 2, 6 (a crystalline solid), had high ICEs in both the rodent and primate models. It significantly decorporated hepatic, renal, and cardiac iron, with no obvious histopathologies. These findings suggest that polyether chain length has a profound effect on ICE, tissue iron decorporation, and ligand physiochemical properties.

  DOI：

  10.1021/jm9018146

文献信息

• DESFERRITHIOCIN POLYETHER ANALOGUES AND USES THEREOF
  申请人：Bergeron, JR. Raymond J.

  公开号：US20120184586A1

  公开（公告）日：2012-07-19

  Desferrithiocin analogues represents by the structural formulae described here, such as formula (I), are useful in treating conditions such as metal overload (e.g., iron overload from transfusion therapy), oxidative stress, and neoplastic and preneoplastic conditions.

  Desferrithiocin类似物由此处描述的结构式代表，例如公式（I），在治疗诸如金属过载（例如输血治疗引起的铁过载）、氧化应激以及肿瘤和癌前病变等疾病方面是有用的。
• US20140343110A1
  申请人：——

  公开号：US20140343110A1

  公开（公告）日：2014-11-20
• USES OF 4'-DESFERRITHIOCIN ANALOGS
  申请人：University of Florida Research Foundation, Inc.

  公开号：US20170209420A1

  公开（公告）日：2017-07-27

  Macular degeneration, closed head injury, stroke, irritable bowel disease, and reperfusion injury are all associated with biological injury due to reactive oxygen species, probably due to focal iron overload in many instances. The present invention provides methods and pharmaceutical compositions for treating these diseases and conditions using desferrithiocin analogs of Formula (I). In certain embodiments, the analogs include a polyether moiety at the 4′-position of the phenyl ring of the compound.
• [EN] USES OF 4'-DESFERRITHIOCIN ANALOGS<br/>[FR] UTILISATION D'ANALOGUES DE 4'-DESFERRITHIOCINE
  申请人：UNIV FLORIDA

  公开号：WO2013090750A1

  公开（公告）日：2013-06-20

  Macular degeneration, closed head injury, stroke, irritable bowel disease, and reperfusion injury are all associated with biological injury due to reactive oxygen species, probably due to focal iron overload in many instances. The present invention provides methods and pharmaceutical compositions for treating these diseases and conditions using desferrithiocin analogs of Formula (I). In certain embodiments, the analogs include a polyether moiety at the 4 '-position of the phenyl ring of the compound.
• The Impact of Polyether Chain Length on the Iron Clearing Efficiency and Physiochemical Properties of Desferrithiocin Analogues
  作者：Raymond J. Bergeron、Neelam Bharti、Jan Wiegand、James S. McManis、Shailendra Singh、Khalil A. Abboud

  DOI：10.1021/jm9018146

  日期：2010.4.8

  (S)-2-(2,4-Dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid (2) was abandoned in clinical trials as an iron chelator for the treatment of iron overload disease because of its nephrotoxicity. However, subsequent investigations revealed that replacing the 4'-(HO) of 2 with a 3,6,9-trioxadecyloxy group, ligand 4, increased iron clearing efficiency (ICE) and ameliorated the renal toxicity of 2. This compelled a closer look at additional polyether analogues, the subject of this work. The 3,6,9,12-tetraoxatridecyloxy analogue of 4, chelator 5, an oil, had twice the ICE in rodents of 4, although its ICE in primates was reduced relative to 4. The corresponding 3,6-dioxaheptyloxy analogue of 2, 6 (a crystalline solid), had high ICEs in both the rodent and primate models. It significantly decorporated hepatic, renal, and cardiac iron, with no obvious histopathologies. These findings suggest that polyether chain length has a profound effect on ICE, tissue iron decorporation, and ligand physiochemical properties.