2-[2-(2-pyridyldithio)ethoxy]-ethanol | 851961-97-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-[2-(2-pyridyldithio)ethoxy]-ethanol
• 英文别名: 2-[2-(Pyridin-2-yldisulfanyl)ethoxy]ethanol；2-[2-(pyridin-2-yldisulfanyl)ethoxy]ethanol
• CAS: 851961-97-2
• 化学式: C₉H₁₃NO₂S₂
• 分子量: 231.34
• InChiKey: CBKZDNCOKXGNHD-UHFFFAOYSA-N

物化性质

• 沸点：
  383.0±40.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  93
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[2-(2-pyridyldithio)ethoxy]-ethanol 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 2-[[3,5-dichloro-4-[2-[2-(2-pyridyldithio)ethoxy]ethoxy]phenyl]amino]-benzoic acid
  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
• 作为产物：
  描述：

  Benzoic acid 2-(2-acetylsulfanyl-ethoxy)-ethyl ester 、 2,2'-二硫二吡啶 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以23%的产率得到2-[2-(2-pyridyldithio)ethoxy]-ethanol
  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

• INJECTABLE DENDRIMER HYDROGEL NANOPARTICLES
  申请人：Kannan Rangaramanujam M.

  公开号：US20130136697A1

  公开（公告）日：2013-05-30

  The invention discloses injectable hydrogels which are in the form of crosslinked nano beads or particle in the size range 5 nm to 10 μm, comprising PAMAM dendrimer with asymmetrical peripheral end groups such that one of the terminal groups is involved in formation of hydrogel and the other in involved in the conjugation of drugs or imaging agents and their methods of preparation. The said gel is formed by reaction of the PAMAM dendrimer with asymmetrical end groups with other polymer wherein the other polymer is selected from the group of linear, branched, hyperbranched or star shaped polymers with functionalized terminal groups. The PAMAM dendrimer with asymmetrical terminal groups consists of a Generation 2 and above PAMAM dendrimer with symmetrical end groups modified using the amino acids or their modified forms. The gel disclosed in the present invention is formed as small crosslinked particles in the size range 25 nm to 10 μm and is suitable for injectable delivery of hydrogel to any of the body orifices, tissues by intramuscular or subcutaneous route and ocular delivery for the purpose of therapeutic treatment and imaging.
• US9526794B2
  申请人：——

  公开号：US9526794B2

  公开（公告）日：2016-12-27
• 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.