ethyl (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate | 887471-66-1

• 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-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate
• 英文别名: (S)-4,5-dihydro-2-[2-hydroxy-4-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]phenyl]-4-methyl-4-thiazolecarboxylic acid ethyl ester；ethyl (4S)-2-[2-hydroxy-4-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]phenyl]-4-methyl-5H-1,3-thiazole-4-carboxylate
• CAS: 887471-66-1
• 化学式: C₂₀H₂₉NO₇S
• 分子量: 427.519
• InChiKey: RRRMPXKFAMEFNO-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate 在 甲醇 、 sodium hydroxide 、 盐酸 、 水 作用下， 反应 16.0h， 以92%的产率得到(S)-4,5-dihydro-2-[2-hydroxy-4-(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：

  地夫立群 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 44.0h， 生成 ethyl (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate
  参考文献：
  名称：

  光学活性ジヒドロチアゾールカルボン酸誘導体の製造法

  摘要：

  提供一种不使用具有遗传毒性试剂，在短工序中制备用作药物的有用光学活性二氢噻唑甲酸衍生物的方法。通过在碱存在下使（S）-4,5-二氢-2-(2,4-二羟基苯基)-4-甲基-4-噻唑甲酸和甘醇单甲醚衍生物反应，制备光学活性二氢噻唑酯衍生物，然后水解得到光学活性二氢噻唑甲酸衍生物，其制备方法由式（4）表示。该制备方法可以在短工序中制备用作药物的有用二氢噻唑甲酸衍生物，减少杂质的副产生。

  公开号：

  JP2017137262A

文献信息

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

  公开号：US20100093812A1

  公开（公告）日：2010-04-15

  A relatively non-toxic desazadesferrithiocin analog having the formula (I): wherein: R 1 , R 2 , R 4 and R 5 may be the same or different and may be H, straight or branched chain alkyl having up to 14 carbon atoms, e.g., methyl, ethyl, propyl and butyl, or arylalkyl wherein the aryl portion is hydrocarbyl and the alkyl portion is straight or branched chain, the arylalkyl group having up to 14 carbon atoms, R2 optionally being alkoxy having up to 14 carbon atoms; R 3 is [(CH 2 ) n —O] x —[(CH 2 ) n —O] y -alkyl; n is, independently, an integer from 1 to 8; x is an integer from 1 to 8; y is an integer from O to 8, and R 3 O may occupy any position on the phenyl ring except the 4-position, or a salt, hydrate or solvate thereof; and methods and compositions for treating the effects of trivalent metal, i.e., iron, overload.

  一种相对无毒的去除铁过载的治疗方法，使用化学式（I）的类去铁血红素衍生物，其中：R1、R2、R4和R5可以相同或不同，可以是氢，直链或支链烷基，碳数不超过14个，例如，甲基，乙基，丙基和丁基，或芳基烷基，其中芳基部分为烃基，烷基部分为直链或支链，芳基烷基的碳数不超过14个，R2可以选择为碳数不超过14个的烷氧基；R3为[(CH2)n-O]x-[(CH2)n-O]y-烷基；n独立地为1到8的整数；x为1到8的整数；y为0到8的整数，R3O可以占据苯环上除4位以外的任何位置，或其盐，水合物或溶剂化物；以及治疗三价金属，即铁，过载的方法和组合物。
• (<i>S</i>)-4,5-Dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic Acid Polyethers:  A Solution to Nephrotoxicity
  作者：Raymond J. Bergeron、Jan Wiegand、James S. McManis、John R. T. Vinson、Hua Yao、Neelam Bharti、James R. Rocca

  DOI：10.1021/jm0508944

  日期：2006.5.1

  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.
• WO2006/107626
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Testing of Non-Nephrotoxic Desazadesferrithiocin Polyether Analogues
  作者：Raymond J. Bergeron、Jan Wiegand、James S. McManis、Neelam Bharti、Shailendra Singh

  DOI：10.1021/jm800154m

  日期：2008.7

  A series of iron-clearing efficiencies (ICEs), ferrokinetics, and toxicity studies for (S)-2-(2,4-dihydroxyphenyl)4,5-dihydro-4-methyl-4-thiazolecarboxylic acid (deferitrin, 1), (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid (2), and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyll-4-methyl-4-thiazolecarboxylic acid (3) are reported. The ICEs in rodents are shown to be dose-dependent and saturable for ligands 2 and 3 and superior to 1. Both polyether analogues in subcutaneous (sc) versus oral (po) administration in rodents and primates demonstrated excellent bioavailability. Finally, in a series of toxicity studies of ligands 1-3, the dosing regimen was shown to have a profound effect in animals treated with ligand 1. When ligand I was given at doses of 237 mu mol/kg/day twice a day (b.i.d.), there was serious proximal tubule damage versus 474,mu mol/kg/day once daily (s.i.d.). With 2 and 3, in iron-overloaded and/or non-iron-loaded rodents, kidney histopathologies remained normal.
• USES OF 4'-DESFERRITHIOCIN ANALOGS
  申请人：University of Florida Research Foundation, Inc.

  公开号：EP2790697B1

  公开（公告）日：2019-10-23