(S)-4,5-dihydro-2-[2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid | 911714-45-9

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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-dioxaheptyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid
• 英文别名: Sp-420；(4S)-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid
• CAS: 911714-45-9
• 化学式: C₁₆H₂₁NO₆S
• 分子量: 355.412
• InChiKey: YASYAEVZKXPYIZ-MRXNPFEDSA-N

物化性质

• 熔点：
  82-83℃ (ethyl acetate hexane )
• 沸点：
  562.2±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：10mg/mL；二甲基亚砜：15mg/mL；乙醇：15mg/mL；乙醇:PBS (pH 7.2) (1:4): 0.2mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-碘代丙烷 、 (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid 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85%的产率得到isopropyl (S)-4,5-dihydro-2-(2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl)-4-methyl-4-thiazolecarboxylate
  参考文献：
  名称：

  The Impact of Polyether Chain Length on the Iron Clearing Efficiency and Physiochemical Properties of Desferrithiocin Analogues

  摘要：

  (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.

  DOI：

  10.1021/jm9018146
• 作为产物：
  描述：

  7-羟基-2,2-二甲基-4H-苯并[D][1,3]二噁英-4-酮 在 氨 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 、 乙腈 为溶剂， 反应 4.5h， 生成 (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid
  参考文献：
  名称：

  DESAZADESFERROTHIOCIN AND DESAZADESFERROTHIOCIN POLYETHER ANALOGUES AS METAL CHELATION AGENTS

  摘要：

  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。

  公开号：

  US20110275636A1

文献信息

• [EN] METABOLICALLY PROGRAMMED METAL CHELATORS AND USES THEREOF<br/>[FR] AGENTS CHÉLATEURS MÉTALLIQUES PROGRAMMÉS MÉTABOLIQUEMENT ET LEURS UTILISATIONS
  申请人：UNIV FLORIDA

  公开号：WO2016176343A1

  公开（公告）日：2016-11-03

  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).

  本发明提供了式（I）的化合物，这些化合物是“代谢程序化”的金属螯合剂，例如，亲脂性、可吸收（例如，口服可吸收）和有效的金属螯合剂，在体内转化为其亲水性、无毒的代谢物。本发明还提供了式（II）的化合物，这些化合物也是“代谢程序化”的金属螯合剂。本发明还提供了包括本文所述化合物的药物组合物、试剂盒、方法和用途。这些化合物、药物组合物、试剂盒和方法可能对治疗或预防疾病（例如，金属过载、氧化应激、糖尿病、肝病、心脏病、癌症、放射损伤、神经系统或神经退行性疾病、弗里德雷希氏共济失调症（FRDA）、黄斑变性、闭合性头部损伤、肠易激综合征、再灌注损伤、金属中毒或传染性疾病）具有用处。
• DESFERRITHIOCIN POLYETHER ANALOGUES AND USES THEREOF
  申请人：Bergeron, JR. Raymond J.

  公开号：US20120184586A1

  公开（公告）日：2012-07-19

  Desferrithiocin analogues represents by the structural formulae described here, such as formula (I), are useful in treating conditions such as metal overload (e.g., iron overload from transfusion therapy), oxidative stress, and neoplastic and preneoplastic conditions.

  Desferrithiocin类似物由此处描述的结构式代表，例如公式（I），在治疗诸如金属过载（例如输血治疗引起的铁过载）、氧化应激以及肿瘤和癌前病变等疾病方面是有用的。
• Desazadesferrothiocin and desazadesferrothiocin polyether analogues as metal chelation agents
  申请人：Malecha James

  公开号：US09045440B2

  公开（公告）日：2015-06-02

  Disclosed herein are new compounds of desazadesferrothiocin polyether (DADFT-PE) analogs, 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.

  本文揭示了新的去氮去硫亚德斯费罗替西汀聚醚（DADFT-PE）类似物化合物，以及包含它们的药物组合物，并将它们应用于金属螯合剂治疗疾病。还提供了在人类或动物主体中螯合铁和其他金属以治疗金属过载和毒性的方法。
• 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。
• 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。