(S)-4,5-dihydro-2-(2-hydroxy-4-(3,6,9,12-tetraoxatridecyloxy)phenyl)-4-methyl-4-thiazolecarboxylic acid | 1204750-62-8

• 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: (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6,9,12-tetraoxatridecyloxy)phenyl)-4-methyl-4-thiazolecarboxylic acid
• 英文别名: (4S)-2-[2-hydroxy-4-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]phenyl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid
• CAS: 1204750-62-8
• 化学式: C₂₀H₂₉NO₈S
• 分子量: 443.518
• InChiKey: BPCDGQUKVKSLPQ-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,5,8,11-四氧杂十三烷-13-基4-甲基苯磺酸酯 在 potassium carbonate 、 sodium iodide 、 sodium hydroxide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 80.5h， 生成 (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6,9,12-tetraoxatridecyloxy)phenyl)-4-methyl-4-thiazolecarboxylic acid
  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

文献信息

• DESAZADESFERROTHIOCIN AND DESAZADESFERROTHIOCIN POLYETHER ANALOGUES AS METAL CHELATION AGENTS
  申请人：Malecha James

  公开号：US20110275636A1

  公开（公告）日：2011-11-10

  Disclosed herein are new compounds of desazadesferrothiocin polyether (DADFT-PE) analogues, as well as pharmaceutical compositions comprising them and their application as metal chelation agents for the treatment of disease. Methods of chelation of iron and other metals in a human or animal subject are also provided for the treatment of metal overload and toxicity.

  本文披露了新的去氮去除铁硫胺聚醚（DADFT-PE）类似物化合物，以及包含它们的药物组合物，以及它们作为金属螯合剂用于治疗疾病的应用。还提供了在人类或动物主体中螯合铁和其他金属的方法，用于治疗金属过载和中毒。
• DESAZADESFERROTHIOCIN ANALOGUES AS METAL CHELATION AGENTS
  申请人：FerroKin BioSciences, Inc.

  公开号：US20150259306A1

  公开（公告）日：2015-09-17

  Disclosed herein are new compounds of desazadesferrothiocin polyether (DADFT-PE) analogues, as well as pharmaceutical compositions comprising them and their application as metal chelation agents for the treatment of disease. Methods of chelation of iron and other metals in a human or animal subject are also provided for the treatment of metal overload and toxicity.

  本文披露了新的去氮去铁硫单环醚（DADFT-PE）类似物化合物，以及包含它们的制药组合物，以及它们作为金属螯合剂用于治疗疾病的应用。还提供了用于治疗人类或动物主体中金属过载和毒性的铁和其他金属螯合方法。
• Remote loading of sparingly water-soluble drugs into lipid vesicles
  申请人：ZONEONE PHARMA, INC.

  公开号：US10004759B2

  公开（公告）日：2018-06-26

  The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading is capability retained. The process is scalable and the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and predictable drug retention when the liposome encapsulated drug is administered in patients.

  本发明提供的脂质体组合物含有用于治疗危及生命的疾病的稀溶性药物。将药物封装在脂质体内的一种优选方法是远程或主动装载。然而，文献中描述的这种方法仅限于可自由溶于水溶液或溶解为水溶性复合物的药物。本发明描述了远程装载低水溶性（<2 mg/mL）药物的组合物和方法。在优选的实施方案中，溶解剂中的药物与水悬浮液中的脂质体混合，使溶解剂的浓度降低到低于其完全溶解药物的能力。这将导致药物沉淀，但远程负载能力得以保留。该工艺具有可扩展性，产生的药物负载脂质体的特点是药物与脂质的比率高，在患者服用脂质体包裹的药物时，药物保留率可预测。
• Remote loading of sparingly water-soluble drugs into liposomes
  申请人：ZONEONE PHARMA, INC.

  公开号：US10722467B2

  公开（公告）日：2020-07-28

  The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading capability is retained. The process is scalable and, in liposomes in which the lipid composition and remote loading agent are optimized, the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and prolonged drug retention when the liposome encapsulated drug is administered to a subject.

  本发明提供的脂质体组合物含有用于治疗危及生命的疾病的稀溶性药物。将药物封装在脂质体内的一种优选方法是远程或主动装载。通过将脂质体悬浮液与药物溶液共混，将药物远程装入含有跨膜电化学梯度的脂质体中，使化合物的中性形式自由进入脂质体并带静电，从而防止反向转移出脂质体。化合物在脂质体内部不断积聚，直到电化学梯度消失或所有药物都被包裹在脂质体中。然而，文献中描述的这一过程仅限于可在水溶液中自由溶解或溶解为水溶性复合物的药物。本发明描述了远程装载低水溶性（<2 mg/mL）药物的组合物和方法。在优选的实施方案中，溶解剂中的药物与水悬浮液中的脂质体混合，使溶解剂的浓度降低到低于其完全溶解药物的能力。这将导致药物沉淀，但远程装载能力得以保留。该工艺具有可扩展性，在脂质组成和远程装载剂都经过优化的脂质体中，所得到的药物负载脂质体的特点是药物与脂质的比率高，当将脂质体包裹的药物施用于受试者时，药物保留时间长。
• 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.