2-[(3,5-二氯-4-甲氧基苯基)氨基]苯甲酸 | 100623-27-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[(3,5-二氯-4-甲氧基苯基)氨基]苯甲酸
• 英文名称: 2-(3,5-dichloro-4-methoxyphenylamino)benzoic acid
• 英文别名: N-(3,5-dichloro-4-methoxy-phenyl)-anthranilic acid；N-(3,5-Dichlor-4-methoxy-phenyl)-anthranilsaeure；2-(3,5-Dichloro-4-methoxyanilino)benzoic acid
• CAS: 100623-27-6
• 化学式: C₁₄H₁₁Cl₂NO₃
• 分子量: 312.152
• InChiKey: UZTXFSDUGHCLPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(3,5-二氯-4-甲氧基苯基)氨基]苯甲酸 在 三氯氧磷 作用下， 生成 1,3,9-trichloro-2-methoxy-acridine
  参考文献：
  名称：

  Munshi; Nargund, Journal of the Indian Chemical Society, 1959, vol. 36, p. 115

  摘要：

  DOI：
• 作为产物：
  描述：

  邻溴苯甲酸甲酯 在 palladium on activated charcoal lithium hydroxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 氢气 、 potassium carbonate 、 caesium carbonate 、 (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 66.0h， 生成 2-[(3,5-二氯-4-甲氧基苯基)氨基]苯甲酸
  参考文献：
  名称：

  Kinetic Stabilization of an Oligomeric Protein by a Single Ligand Binding Event

  摘要：

  Protein native state stabilization imposed by small molecule binding is an attractive strategy to prevent the misfolding and misassembly processes associated with amyloid diseases. Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation before misassembly of a partially denatured monomer ensues. Selective stabilization of the native TTR tetramer over the dissociative transition state by small molecule binding to both thyroxine binding sites raises the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Assessing the amyloidogenicity of a TTR tetramer having only one amyloidogenesis inhibitor (1) bound is challenging because the two small molecule binding constants are generally not distinct enough to allow for the exclusive formation of (TTRI)-I-. in solution to the exclusion of (TTRI2)-I-. and unliganded TTR. Herein, we report a method to tether one fibril formation inhibitor to TTR by disulfide bond formation. Occupancy of only one of the two thyroxine binding sites is sufficient to inhibit tetramer dissociation in 6.0 M urea and amyloidogenesis under acidic conditions by imposing kinetic stabilization on the entire tetramer. The sufficiency of single occupancy for stabilizing the native state of TTR provides the incentive to search for compounds displaying striking negative binding cooperativity (e.g., K-d1 in nanomolar range and K-d2 in the micromolar to millimolar range), enabling lower doses of inhibitor to be employed in the clinic, mitigating potential side effects.

  DOI：

  10.1021/ja042929f

文献信息

• COMPOUND AND USE THEREOF IN THE TREATMENT OF AMYLOIDOSIS
  申请人：PEPYS Mark Brian

  公开号：US20100249233A1

  公开（公告）日：2010-09-30

  The present invention relates to compounds of formula (I) for stabilizing the tetrameric form of transthyretin, compounds for use in the treatment or prevention of amyloidosis, and agents and medicaments comprising such compounds. wherein X, Y, R 1 , R 2 , R 3 , R 4 , m, n, p, q, and the linker are as defined herein.

  本发明涉及式（I）的化合物，用于稳定甲状腺素转运蛋白四聚体形式，用于治疗或预防淀粉样变性的化合物，以及包含这些化合物的药剂和药物，其中X，Y，R1，R2，R3，R4，m，n，p，q，和连接物如本文所定义。
• US8236984B2
  申请人：——

  公开号：US8236984B2

  公开（公告）日：2012-08-07
• Kinetic Stabilization of an Oligomeric Protein by a Single Ligand Binding Event
  作者：R. Luke Wiseman、Steven M. Johnson、Matthew S. Kelker、Ted Foss、Ian A. Wilson、Jeffery W. Kelly

  DOI：10.1021/ja042929f

  日期：2005.4.1

  Protein native state stabilization imposed by small molecule binding is an attractive strategy to prevent the misfolding and misassembly processes associated with amyloid diseases. Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation before misassembly of a partially denatured monomer ensues. Selective stabilization of the native TTR tetramer over the dissociative transition state by small molecule binding to both thyroxine binding sites raises the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Assessing the amyloidogenicity of a TTR tetramer having only one amyloidogenesis inhibitor (1) bound is challenging because the two small molecule binding constants are generally not distinct enough to allow for the exclusive formation of (TTRI)-I-. in solution to the exclusion of (TTRI2)-I-. and unliganded TTR. Herein, we report a method to tether one fibril formation inhibitor to TTR by disulfide bond formation. Occupancy of only one of the two thyroxine binding sites is sufficient to inhibit tetramer dissociation in 6.0 M urea and amyloidogenesis under acidic conditions by imposing kinetic stabilization on the entire tetramer. The sufficiency of single occupancy for stabilizing the native state of TTR provides the incentive to search for compounds displaying striking negative binding cooperativity (e.g., K-d1 in nanomolar range and K-d2 in the micromolar to millimolar range), enabling lower doses of inhibitor to be employed in the clinic, mitigating potential side effects.
• Munshi; Nargund, Journal of the Indian Chemical Society, 1959, vol. 36, p. 115
  作者：Munshi、Nargund

  DOI：——

  日期：——