isopropyl (S)-2-(2,5-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate | 945635-16-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: isopropyl (S)-2-(2,5-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate
• 英文别名: (S)-isopropyl 2-(2,5-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate；propan-2-yl (4S)-2-(2,5-dihydroxyphenyl)-4-methyl-5H-1,3-thiazole-4-carboxylate
• CAS: 945635-16-5
• 化学式: C₁₄H₁₇NO₄S
• 分子量: 295.359
• InChiKey: CHHWPIUDPJGTRK-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  isopropyl (S)-2-(2,5-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate 在 甲醇 、 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 39.0h， 生成 (S)-4,5-dihydro-2-[2-hydroxy-5-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid
  参考文献：
  名称：

  WO2008/115433

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid 、 2-碘代丙烷 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以92%的产率得到isopropyl (S)-2-(2,5-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate
  参考文献：
  名称：

  Impact of the 3,6,9-Trioxadecyloxy Group on Desazadesferrithiocin Analogue Iron Clearance and Organ Distribution

  摘要：

  The impact of introducing a 3,6,9-trioxadecyloxyl group at various positions of the desazadesferrithiocin (DADFT) aromatic ring on iron clearance and organ distribution is described. Three DADFT polyethers are evaluated: (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE, 3], (S)-4,5-dihydro-2-[2-hydroxy-5-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-5'-(HO)-DADFT-PE, 6], and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE, 9]. The iron-clearing efficiency (ICE) in rodents and primates is shown to be very sensitive to which positional isomer is evaluated, as is the organ distribution in rodents. The polyethers had uniformly higher ICEs than their corresponding parent ligands in rodents, consistent with in vivo ligand-serum albumin binding studies. Ligand 9 is the most active polyether analogue in rodents and is also very effective in primates, suggesting a higher index of success in humans. In addition, this analogue is also shown to clear more iron in the urine of the primates than many of the other chelators. If this trend were also observed in patients, it would facilitate iron-balance studies in a clinical setting.

  DOI：

  10.1021/jm070214s

文献信息

• 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?.