isopropyl (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate | 887471-64-9

• 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-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate
• 英文别名: (S)-4'-(HO)-DADFT-iPrE；propan-2-yl (4S)-2-(2,4-dihydroxyphenyl)-4-methyl-5H-1,3-thiazole-4-carboxylate
• CAS: 887471-64-9
• 化学式: C₁₄H₁₇NO₄S
• 分子量: 295.359
• InChiKey: NEKROIYNASGZFR-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-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 17.0h， 生成 (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid
  参考文献：
  名称：

  (S)-4,5-Dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic Acid Polyethers:  A Solution to Nephrotoxicity

  摘要：

  Previous studies revealed that within a family of ligands the more lipophilic chelators have better iron-clearing efficiency. The larger the log P-app value of the compound, the better the iron-clearing efficiency. What is also clear from the data is that although the relative effects of log P-app changes are essentially the same through different families, there are differences in absolute value between families. However, there also exists a second, albeit somewhat more disturbing, relationship. In all sets of ligands, the most lipophilic chelator is always the most toxic. The current study focuses on designing ligands that balance the lipophilicity/ toxicity problem while iron-clearing efficiency is maintained. Earlier studies with (S)-4,5-dihydro-2-(2-hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4-(CH3O)-DADFT,6] indicated that this methyl ether was a ligand with excellent iron-clearing efficiency in both rodents and primates; however, it was too toxic. On the basis of this finding, a less lipophilic, more water-soluble ligand than 6 was assembled, (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4(HO)-DADFT-PE,11], a polyether analogue, along with its ethyl and isopropyl esters. The parent polyether and its isopropyl and ethyl esters were all shown to be highly efficient iron chelators in both rodents and primates. A comparison of 11 in rodents with the desferrithiocin analogue (S)-4,5-dihydro-2-(2,4dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4-(HO)-DADFT, 1] revealed the polyether to be more tolerable, achieving higher concentrations in the liver and significantly lower concentrations in the kidney. The lower renal drug levels are in keeping with the profound difference in the architectural changes seen in the kidney of rodents given 1 versus those treated with 11.

  DOI：

  10.1021/jm0508944
• 作为产物：
  描述：

  2-碘代丙烷 、 地夫立群 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 336.0h， 以99%的产率得到isopropyl (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylate
  参考文献：
  名称：

  (S)-4,5-Dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic Acid Polyethers:  A Solution to Nephrotoxicity

  摘要：

  Previous studies revealed that within a family of ligands the more lipophilic chelators have better iron-clearing efficiency. The larger the log P-app value of the compound, the better the iron-clearing efficiency. What is also clear from the data is that although the relative effects of log P-app changes are essentially the same through different families, there are differences in absolute value between families. However, there also exists a second, albeit somewhat more disturbing, relationship. In all sets of ligands, the most lipophilic chelator is always the most toxic. The current study focuses on designing ligands that balance the lipophilicity/ toxicity problem while iron-clearing efficiency is maintained. Earlier studies with (S)-4,5-dihydro-2-(2-hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4-(CH3O)-DADFT,6] indicated that this methyl ether was a ligand with excellent iron-clearing efficiency in both rodents and primates; however, it was too toxic. On the basis of this finding, a less lipophilic, more water-soluble ligand than 6 was assembled, (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4(HO)-DADFT-PE,11], a polyether analogue, along with its ethyl and isopropyl esters. The parent polyether and its isopropyl and ethyl esters were all shown to be highly efficient iron chelators in both rodents and primates. A comparison of 11 in rodents with the desferrithiocin analogue (S)-4,5-dihydro-2-(2,4dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4-(HO)-DADFT, 1] revealed the polyether to be more tolerable, achieving higher concentrations in the liver and significantly lower concentrations in the kidney. The lower renal drug levels are in keeping with the profound difference in the architectural changes seen in the kidney of rodents given 1 versus those treated with 11.

  DOI：

  10.1021/jm0508944

文献信息

• DESFERRITHIOCIN POLYETHER ANALOGUES
  申请人：University of Florida Research Foundation, Inc.

  公开号：EP3190106A1

  公开（公告）日：2017-07-12

  Compounds represented by structural formulas described herein, such as Structural Formula (I): are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.

  本文所述结构式（如结构式 (I)）所代表的化合物可用于治疗金属超载、氧化应激、肿瘤和肿瘤前病变等病症。
• Desferrithiocin polyether analogues
  申请人：Bergeron Raymond J.

  公开号：US20080214630A1

  公开（公告）日：2008-09-04

  Compounds represented by structural formulas described herein, such as Structural Formula (I): or a pharmaceutically acceptable salt thereof are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.
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