(S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid | 917955-19-2

• 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-(2,5-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid
• 英文别名: (4S)-2-(2,5-dihydroxyphenyl)-4-methyl-5H-1,3-thiazole-4-carboxylic acid
• CAS: 917955-19-2
• 化学式: C₁₁H₁₁NO₄S
• 分子量: 253.279
• InChiKey: ZGWGIYLDFQYMED-LLVKDONJSA-N

物化性质

• 熔点：
  223-224.5 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  543.3±60.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid 在 甲醇 、 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 111.0h， 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：
• 作为产物：
  描述：

  2,5-二甲氧基苯甲腈 在 三溴化硼 、 碳酸氢钠 作用下， 以 甲醇 、 phosphate buffer 、 二氯甲烷 为溶剂， 反应 58.0h， 生成 (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid
  参考文献：
  名称：

  The Design, Synthesis, and Evaluation of Organ-Specific Iron Chelators

  摘要：

  A series of iron chelators, three (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid (DADFT) and three (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-thiazolecarboxylic acid (DADMDFT) analogues are synthesized and assessed for their lipophilicity (log Papp), iron-clearing efficiency (ICE) in rodents and iron-loaded primates (Cebus apella), toxicity in rodents, and organ distribution in rodents. The results lead to a number of generalizations useful in chelator design strategies. In rodents, while log Papp is a good predictor of a chelator's ICE, chelator liver concentration is a better tool. In primates, log Papp is a good predictor of ICE, but only when comparing structurally very similar chelators. There is a profound difference in toxicity between the DADMDFT and DADFT series: DADMDFTs are less toxic. Within the DADFT family of ligands, the more lipophilic ligands are generally more toxic. Lipophilicity can have a profound effect on ligand organ distribution, and ligands can thus be targeted to organs compromised in iron overload disease, for example, the heart.

  DOI：

  10.1021/jm0608816

文献信息

• Iron binding agents
  申请人：University of Florida

  公开号：US20030083349A1

  公开（公告）日：2003-05-01

  Composition, article of manufacture for and method of treating malaria in a human having an infestation of Plasmodium protozoans are described. The method comprises administering a therapeutically-effective amount of a compound of formula (I) or (IV), i.e. sufficient quantity to reduce the population of Plasmodium. The composition of the invention is a compound of formula (I) or (IV) with a pharmaceutical excipient. The article of manufacture is the composition in combination with labeling for treating malaria. The substituents are detailed in the specification.

  本发明涉及一种用于治疗人类患有疟原虫感染的组合物、制品及方法。该方法包括给予化合物(I)或(IV)的治疗有效量，即足够减少疟原虫数量。本发明的组合物是一种含有药用辅料的化合物(I)或(IV)。制品是该组合物与用于治疗疟疾的标签的组合。取代基详见规范。
• 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。
• Antimalarial agents
  申请人：UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC.

  公开号：EP1488791A2

  公开（公告）日：2004-12-22

  Composition, article of manufacture for and method of treating malaria in a human having an infestation of Plasmodium protozoans are described. The method comprises administering a therapeutically effective amount of a compound of formula (I) or (IV), i.e., sufficient quantity to reduce the population of Plasmodium. The composition of the invention is a compound of formula (I) or (IV) with a pharmaceutical excipient. The article of manufacture is the composition in combination with labelling for treating malaria. The substituents are detailed in the specification.

  本发明描述了用于治疗原生动物疟原虫感染的人类疟疾的组合物、制造品和方法。该方法包括施用治疗有效量的式（I）或（IV）化合物，即足以减少疟原虫数量的量。本发明的组合物是含有药用赋形剂的式 (I) 或 (IV) 化合物。制成品是该组合物与用于治疗疟疾的标签相结合。取代基详见说明书。
• WO2008/115433
  申请人：——

  公开号：——

  公开（公告）日：——
• Desferrithiocin Analogues and Nephrotoxicity
  作者：Raymond J. Bergeron、Jan Wiegand、James S. McManis、Neelam Bharti、Shailendra Singh

  DOI：10.1021/jm8003398

  日期：2008.10.9

  The syntheses of a series of 4'-O-alkylated (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4-thiazole-carboxylic acid and 5'-O-alkylated (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazoleearboxylic acid ligands are described. Their partition between octanol and water, 109 Pap,, is determined, along with their iron-clearing efficiency (ICE) in both non-iron-overloaded, bile duct-cannulated rodents and in iron-overloaded primates. The ligand-promoted biliary ferrokinetics in rats are described for each of the chelators. Plots of log P-app versus ICE in a rodent model for both the 4'-O-alkylated 2,4-dihydroxy and 5'-O-alkylated 2,5-dihydroxy series produced an inverse parabola plot with r(2) values of 0.97 and 0.81, respectively. The plots indicate an optimum log P-app/ICE relationship. Because of the nature of the data spread in the 4'-O-alkylated 2,4-dihydroxy series, it will be used to help assess the origin of nephrotoxicity in desferrithiocin analogues: is toxicity simply related to lipophilicity, ICE, or a combination of these properties?.