(S)-4,5-dihydro-2-(4-ethoxy-2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid | 1067642-86-7

• 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: (S)-4,5-dihydro-2-(4-ethoxy-2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid
• 英文别名: (4S)-2-(4-ethoxy-2-hydroxyphenyl)-4-methyl-5H-1,3-thiazole-4-carboxylic acid
• CAS: 1067642-86-7
• 化学式: C₁₃H₁₅NO₄S
• 分子量: 281.332
• InChiKey: GXBZCUOMAJETCT-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl (S)-4,5-dihydro-2-(4-ethoxy-2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylate 在 甲醇 、 sodium hydroxide 、 水 作用下， 反应 18.0h， 以90%的产率得到(S)-4,5-dihydro-2-(4-ethoxy-2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid
  参考文献：
  名称：

  Desferrithiocin Analogues and Nephrotoxicity

  摘要：

  The syntheses of a series of 4'-O-alkylated (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4-thiazole-carboxylic acid and 5'-O-alkylated (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazoleearboxylic acid ligands are described. Their partition between octanol and water, 109 Pap,, is determined, along with their iron-clearing efficiency (ICE) in both non-iron-overloaded, bile duct-cannulated rodents and in iron-overloaded primates. The ligand-promoted biliary ferrokinetics in rats are described for each of the chelators. Plots of log P-app versus ICE in a rodent model for both the 4'-O-alkylated 2,4-dihydroxy and 5'-O-alkylated 2,5-dihydroxy series produced an inverse parabola plot with r(2) values of 0.97 and 0.81, respectively. The plots indicate an optimum log P-app/ICE relationship. Because of the nature of the data spread in the 4'-O-alkylated 2,4-dihydroxy series, it will be used to help assess the origin of nephrotoxicity in desferrithiocin analogues: is toxicity simply related to lipophilicity, ICE, or a combination of these properties?.

  DOI：

  10.1021/jm8003398

文献信息

• METABOLICALLY PROGRAMMED METAL CHELATORS AND USES THEREOF
  申请人：University Of Florida Research Foundation, Incorporated

  公开号：US20180140581A1

  公开（公告）日：2018-05-24

  The present invention provides compounds of Formula (I), which are “metabolically programmed” metal chelators, e.g., lipophilic, absorbable (e.g., orally absorbable), and effective metal chelators that are converted in vivo to their hydrophilic, nontoxic metabolites. The present invention also provides compounds of Formula (II), which are also “metabolically programmed” metal chelators. The invention also provides pharmaceutical compositions, kits, methods, and uses that include a compound described herein. The compounds, pharmaceutical compositions, kits, and methods may be useful in treating or preventing a disease (e.g., metal overload, oxidative stress, diabetes, liver disease, heart disease, cancer, radiation injury, neurological or neurodegenerative disorder, Friedreich's ataxia (FRDA), macular degeneration, closed head injury, irritable bowel disease, reperfusion injury, metal poisoning, or infectious disease).
• Desferrithiocin Analogues and Nephrotoxicity
  作者：Raymond J. Bergeron、Jan Wiegand、James S. McManis、Neelam Bharti、Shailendra Singh

  DOI：10.1021/jm8003398

  日期：2008.10.9

  The syntheses of a series of 4'-O-alkylated (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4-thiazole-carboxylic acid and 5'-O-alkylated (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazoleearboxylic acid ligands are described. Their partition between octanol and water, 109 Pap,, is determined, along with their iron-clearing efficiency (ICE) in both non-iron-overloaded, bile duct-cannulated rodents and in iron-overloaded primates. The ligand-promoted biliary ferrokinetics in rats are described for each of the chelators. Plots of log P-app versus ICE in a rodent model for both the 4'-O-alkylated 2,4-dihydroxy and 5'-O-alkylated 2,5-dihydroxy series produced an inverse parabola plot with r(2) values of 0.97 and 0.81, respectively. The plots indicate an optimum log P-app/ICE relationship. Because of the nature of the data spread in the 4'-O-alkylated 2,4-dihydroxy series, it will be used to help assess the origin of nephrotoxicity in desferrithiocin analogues: is toxicity simply related to lipophilicity, ICE, or a combination of these properties?.