2-hydroxy-5-((4-oxo-2-thioxo-3-(2-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid | 1073612-70-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-hydroxy-5-((4-oxo-2-thioxo-3-(2-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid
• 英文别名: 2-Hydroxy-5-[[4-oxo-2-sulfanylidene-3-[2-(trifluoromethyl)phenyl]-1,3-thiazolidin-5-ylidene]methyl]benzoic acid；2-hydroxy-5-[[4-oxo-2-sulfanylidene-3-[2-(trifluoromethyl)phenyl]-1,3-thiazolidin-5-ylidene]methyl]benzoic acid
• CAS: 1073612-70-0
• 化学式: C₁₈H₁₀F₃NO₄S₂
• 分子量: 425.409
• InChiKey: DQTXDKWFCXXIIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-Sulfanylidene-3-[2-(trifluoromethyl)phenyl]-1,3-thiazolidin-4-one 、 5-甲酰水杨酸 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2-hydroxy-5-((4-oxo-2-thioxo-3-(2-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid
  参考文献：
  名称：

  Thiazolidinone CFTR inhibitors with improved water solubility identified by structure–activity analysis

  摘要：

  The thiazolidinone 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) inhibits cystic fibrosis transmembrane conductance regulator ( CFTR) chloride channel conductance with submicromolar affinity and blocks cholera toxin-induced intestinal fluid secretion. Fifty-eight CFTRinh-172 analogs were synthesized to identify CFTR inhibitors with improved water solubility, exploring modi. cations in its two phenyl rings, thiazolidinone core, and core-phenyl connectors. Greatest CFTR inhibition potency was found for 3-CF3 and polar group-substituted-phenyl rings, and a thiazolidinone core. Two compounds with similar to 1 mu M CFTR inhibition potency and solubility >180 mu M(>10-fold more than CFTRinh-172) were identified: Tetrazolo-172, containing 4-tetrazolophenyl in place of 4-carboxyphenyl, and Oxo-172, containing thiazolidinedione in place of the thiazolidinone core. These water soluble thiazolidinone analogs had low cellular toxicity. The improved water solubility of Tetrazolo- and Oxo-172 make them potential lead candidates for therapy of secretory diarrheas and polycystic kidney disease. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.044

文献信息

• WATER SOLUBLE SMALL MOLECULE INHIBITORS OF THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
  申请人：Verkman Alan S.

  公开号：US20110105565A1

  公开（公告）日：2011-05-05

  Provided herein are highly water soluble, thiazolidinone derivative compounds and glycine hydrazide derivative compounds that inhibit the ion transport activity of the cystic fibrosis transmembrane conductance regulator (CFTR). The compounds, and compositions comprising the compounds, described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, secretory diarrhea. The compounds may also be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

  本文提供了高度水溶性的噻唑啉酮衍生物化合物和甘氨酸酰肼衍生物化合物，这些化合物抑制了囊性纤维化跨膜传导调节器（CFTR）的离子传输活性。本文描述的化合物和含有这些化合物的组合物对于治疗与CFTR活性异常增加相关的疾病、紊乱和疾病、紊乱和条件的后遗症非常有用，例如分泌性腹泻。这些化合物也可用于抑制或预防多囊肾病患者囊肿的扩张或形成。
• Cystic fibrosis transmembrane conductance regulator protein inhibitors and uses thereof
  申请人：——

  公开号：US20040235800A1

  公开（公告）日：2004-11-25

  The invention provides compositions, pharmaceutical preparations and methods for inhibition of cystic fibrosis transmembrane conductance regulator protein (CFTR) that are useful for the study and treatment of CFTR-mediated diseases and conditions. The compositions and pharmaceutical preparations of the invention may comprise one or more thiazolidinone compounds, and may additionally comprise one or more pharmaceutically acceptable carriers, excipients and/or adjuvants. The methods of the invention comprise, in certain embodiments, administering to a patient suffering from a CFTR-mediated disease or condition, an efficacious amount of a thiazolidinone compound. In other embodiments the invention provides methods of inhibiting CFTR that comprise contacting cells in a subject with an effective amount of a thiazolidinone compound. In addition, the invention features a non-human animal model of CFTR-mediated disease which model is produced by administration of a thiazolidinone compound to a non-human animal in an amount sufficient to inhibit CFTR.

  本发明提供了用于抑制囊性纤维化跨膜传导调节蛋白（CFTR）的组合物、制药制剂和方法，这些组合物、制药制剂和方法对于研究和治疗CFTR介导的疾病和病况非常有用。本发明的组合物和制药制剂可以包括一种或多种噻唑烷酮化合物，并且可以另外包括一种或多种药学上可接受的载体、赋形剂和/或佐剂。本发明的方法包括，在某些实施例中，向患有CFTR介导的疾病或病况的患者施用有效量的噻唑烷酮化合物。在其他实施例中，本发明提供了抑制CFTR的方法，包括用有效量的噻唑烷酮化合物接触受体内细胞。此外，本发明还提供了一种CFTR介导的疾病的非人类动物模型，该模型通过向非人类动物施用足以抑制CFTR的噻唑烷酮化合物产生。
• CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN INHIBITORS AND USES THEREOF
  申请人：Verkman Alan

  公开号：US20080064666A1

  公开（公告）日：2008-03-13

  The invention provides compositions, pharmaceutical preparations and methods for inhibition of cystic fibrosis transmembrane conductance regulator protein (CFTR) that are useful for the study and treatment of CFTR-mediated diseases and conditions. The compositions and pharmaceutical preparations of the invention may comprise one or more thiazolidinone compounds, and may additionally comprise one or more pharmaceutically acceptable carriers, excipients and/or adjuvants. The methods of the invention comprise, in certain embodiments, administering to a patient suffering from a CFTR-mediated disease or condition, an efficacious amount of a thiazolidinone compound. In other embodiments the invention provides methods of inhibiting CFTR that comprise contacting cells in a subject with an effective amount of a thiazolidinone compound. In addition, the invention features a non-human animal model of CFTR-mediated disease which model is produced by administration of a thiazolidinone compound to a non-human animal in an amount sufficient to inhibit CFTR.

  本发明提供了抑制囊性纤维化跨膜传导调节蛋白（CFTR）的组合物、药物制剂和方法，这些组合物、药物制剂和方法对于研究和治疗CFTR介导的疾病和病况非常有用。本发明的组合物和药物制剂可以包括一个或多个噻唑烷酮化合物，并且可以另外包括一个或多个药用载体、辅料和/或佐剂。本发明的方法包括，在某些实施例中，向患有CFTR介导的疾病或病况的患者施用有效量的噻唑烷酮化合物。在其他实施例中，本发明提供了抑制CFTR的方法，包括用有效量的噻唑烷酮化合物接触患者细胞。此外，本发明还提供了一种CFTR介导的疾病的非人类动物模型，该模型通过向非人类动物施用足以抑制CFTR的噻唑烷酮化合物而产生。
• EP1549321A4
  申请人：——

  公开号：EP1549321A4

  公开（公告）日：2007-05-23
• US7235573B2
  申请人：——

  公开号：US7235573B2

  公开（公告）日：2007-06-26