N-(2-(5-chloro-2-methoxyphenylamino)-4'-methyl-4,5'-bithiazol-2'-yl)pivalamide | 958941-60-1

• 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: N-(2-(5-chloro-2-methoxyphenylamino)-4'-methyl-4,5'-bithiazol-2'-yl)pivalamide
• 英文别名: N-(5-(2-(5-chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide；15JF；CFTR corrector 12；N-[5-[2-(5-chloro-2-methoxyanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]-2,2-dimethylpropanamide
• CAS: 958941-60-1
• 化学式: C₁₉H₂₁ClN₄O₂S₂
• 分子量: 436.986
• InChiKey: XERLNCVIGMCAMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  C₁₄H₁₃ClN₄OS₂ 、 三甲基乙酰氯 在 三乙胺 作用下， 以 氯仿 为溶剂， 生成 N-(2-(5-chloro-2-methoxyphenylamino)-4'-methyl-4,5'-bithiazol-2'-yl)pivalamide
  参考文献：
  名称：

  4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing

  摘要：

  The synthesis and Delta F508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human Delta F508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.037

文献信息

• Compounds Having Activity in Correcting Mutant-CFTR Processing and Uses Thereof
  申请人：Kurth Mark J.

  公开号：US20100273839A1

  公开（公告）日：2010-10-28

  The invention provides compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The compositions pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The compositions and pharmaceutical preparations of the invention may comprise one or more bithiazole-containing compounds of the invention, or an analog or derivative thereof.

  本发明提供了用于增加突变囊性纤维化跨膜传导调节因子蛋白（突变CFTR）活性的组合物、制药制剂和方法。该组合物、制药制剂和方法可用于突变CFTR相关的疾病的研究和治疗，如囊性纤维化。本发明的组合物和制药制剂可以包含本发明的一种或多种双噻唑含有化合物，或其类似物或衍生物。
• Rapid quantitative assay to measure CFTR function in a primary intestinal culture model
  申请人：UMC Utrecht Holding B.V.

  公开号：US10006904B2

  公开（公告）日：2018-06-26

  The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.

  本发明涉及一种检测方法，用于诊断影响液体吸收或分泌的疾病或痛苦，或研究一种或多种治疗疾病或痛苦的药物的有效性，其中检测方法包括测量一种或多种有机体的肿胀。
• Identifying drug candidates for treating polycystic kidney disease using organoids generated from primary cells
  申请人：UMC Utrecht Holding B.V.

  公开号：US11035852B2

  公开（公告）日：2021-06-15

  The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.

  本发明涉及一种检测方法，用于诊断影响液体吸收或分泌的疾病或痛苦，或研究一种或多种治疗疾病或痛苦的药物的有效性，其中检测方法包括测量一种或多种有机体的肿胀。
• Combination treatment of sarcoglycanopathies
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)

  公开号：US11298348B2

  公开（公告）日：2022-04-12

  Sarcoglycanopathies are autosomal recessive diseases caused by mutations in the one of the genes coding for any sarcoglycans (SG). The inventors previously showed that the application of small molecules developed to rescue ΔF508-CFTR trafficking, and known as CFTR correctors, improved the maturation of several α-sarcoglycan mutants that were consequently rescued at the plasma membrane (WO 014086687). Now, the inventors show that some specific CFTR correctors provide additive and even synergic effect when administered in combination.

  肌糖蛋白病是一种常染色体隐性遗传病，由编码肌糖蛋白（SG）的一个基因突变引起。本发明人之前的研究表明，应用为挽救ΔF508-CFTR转运而开发的小分子（称为CFTR校正剂），可以改善几种α-肌糖突变体的成熟，从而在质膜上得到挽救（WO 014086687）。现在，本发明者证明，某些特定的 CFTR 校正器在联合使用时可产生叠加甚至协同效应。
• A RAPID QUANTITATIVE ASSAY TO MEASURE CFTR FUNCTION IN A PRIMARY INTESTINAL CULTURE MODEL
  申请人：UMC Utrecht Holding B.V.

  公开号：EP2795322B1

  公开（公告）日：2015-12-09