(S)-4,5-dihydro-2-[2-hydroxy-5-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid | 945635-14-3

• 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-5-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid
• 英文别名: (S)-4,5-Dihydro-2-[2-hydroxy-5-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic Acid；(4S)-2-[2-hydroxy-5-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]phenyl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid
• CAS: 945635-14-3
• 化学式: C₁₈H₂₅NO₇S
• 分子量: 399.465
• InChiKey: IBGURTCTZFSAPS-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-4,5-dihydro-2-[2-hydroxy-5-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid 、 sodium hydroxide 以 H₂₀ 为溶剂， 生成 sodium;(4S)-2-[2-hydroxy-5-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]phenyl]-4-methyl-5H-1,3-thiazole-4-carboxylate
  参考文献：
  名称：

  WO2008/115433

  摘要：

  公开号：
• 作为产物：
  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：

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。
• Desferrithiocin polyether analogues
  申请人：University of Florida Research Foundation, Inc.

  公开号：US08324397B2

  公开（公告）日：2012-12-04

  A relatively non-toxic desazadesferrithiocin analog having the formula (I): wherein: R1, R2, R4 and R5 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; R3 is [(CH2)n—O]x—[(CH2)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 R3O 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.

  一种相对低毒的去氧代硫代铁胺类似物，其化学式为（I）：其中：R1、R2、R4和R5可以相同也可以不同，可以是氢、直链或支链烷基，具有14个碳原子，例如，甲基、乙基、丙基和丁基，或芳基烷基，其中芳基部分是烃基，烷基部分是直链或支链，芳基烷基组分具有14个碳原子，R2可选为具有14个碳原子的烷氧基；R3为[(CH2)n—O]x—[(CH2)n—O]y-烷基；n独立地是1到8的整数；x是1到8的整数；y是0到8的整数，且R3O可以占据苯环上除4位以外的任何位置，或其盐、水合物或溶剂合物；以及治疗三价金属，即铁，过载的方法和组合物。
• Impact of the 3,6,9-Trioxadecyloxy Group on Desazadesferrithiocin Analogue Iron Clearance and Organ Distribution
  作者：Raymond J. Bergeron、Jan Wiegand、Neelam Bharti、Shailendra Singh、James R. Rocca

  DOI：10.1021/jm070214s

  日期：2007.7.1

  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.
• NOVEL SALTS AND POLYMORPHS OF DESAZADESFERROTHIOCIN POLYETHER ANALOGUES AS METAL CHELATION AGENTS
  申请人：Tapper Amy E.

  公开号：US20100137383A1

  公开（公告）日：2010-06-03

  Disclosed herein are new salts and polymorphs of desazadesferrithiocin 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.
• NOVEL SALTS AND POLYMORPHS OF DESAZADESFERRITHIOCIN POLYETHER ANALOGUES AS METAL CHELATION AGENTS
  申请人：Tapper Amy E.

  公开号：US20120202857A1

  公开（公告）日：2012-08-09

  Disclosed herein are new salts and polymorphs of desazadesferrithiocin 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.