3-(dimethylamino)-5-(ethoxycarbonyl)benzoic acid | 1255928-47-2

• 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: 3-(dimethylamino)-5-(ethoxycarbonyl)benzoic acid
• 英文别名: 3-(dimethylamino)-5-ethoxycarbonylbenzoic acid
• CAS: 1255928-47-2
• 化学式: C₁₂H₁₅NO₄
• 分子量: 237.255
• InChiKey: YUYDQSJENOVOLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(dimethylamino)-5-(ethoxycarbonyl)benzoic acid 在 盐酸 、 4-二甲氨基吡啶 、 N-氯代丁二酰亚胺 、 硼烷四氢呋喃络合物 、 水 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 sodium hydroxide 、 亚磷酸三乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 80.5h， 生成 4-fluorophenyl (E)-3-(dimethylamino)-5-(4-hydroxy-3,5-dimethylstyryl)benzoate
  参考文献：
  名称：

  [EN] SMALL MOLECULES THAT COVALENTLY MODIFY TRANSTHYRETIN
  [FR] PETITES MOLÉCULES QUI MODIFIENT DE FAÇON COVALENTE LA TRANSTHYRÉTINE

  摘要：

  公开号：

  WO2011075210A3
• 作为产物：
  描述：

  聚合甲醛 、 3-氨基-5-(甲氧基羰基)苯甲酸 在 sodium cyanoborohydride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 以2.1 g的产率得到3-(dimethylamino)-5-(ethoxycarbonyl)benzoic acid
  参考文献：
  名称：

  A Stilbene That Binds Selectively to Transthyretin in Cells and Remains Dark until It Undergoes a Chemoselective Reaction To Create a Bright Blue Fluorescent Conjugate

  摘要：

  We describe a non-fluorescent, second generation stilbene that very selectively binds to transthyretin in complex biological environments and remains dark until it chemoselectively reacts with the pK(a)-perturbed Lys-15 epsilon-amino group of transthyretin to form a bright blue fluorescent conjugate. Stilbene A2 is mechanistically unusual in that it remains non-fluorescent in cell lysates lacking transthyretin, even though there is likely some proteome binding. Thus, it is especially useful for cellular imaging, as background fluorescence is undetectable until A2 reacts with transthyretin. The mechanistic basis for the effective lack of environment-sensitive fluorescence of A2 when bound to, but before reacting with, transthyretin is reported. Stilbene A2 exhibits sufficiently rapid transthyretin conjugation kinetics at 37 degrees C to enable pulse-chase experiments to be performed, in this case demonstrating that transthyretin is secreted from HeLa cells. As the chase compound, we employed Cl, a cell-permeable, highly selective, non-covalent, transthyretin-binding dihydrostilbene that cannot become fluorescent. The progress reported is viewed as a first and necessary step toward our long-term goal of creating a one-chain, one-binding-site transthyretin tag, whose fluorescence can be regulated by adding A2 or an analogous molecule. Fusing proteins of interest to a one-chain, one-binding-site transthyretin tag regulated by A2 should be useful for studying folding, trafficking, and degradation in the cellular secretory pathway, utilizing pulse-chase experiments. Immediate applications of A2 include utilizing its conjugate fluorescence to quantify transthyretin concentration in human plasma, reflecting nutritional status, and determining the binding stoichiometry of kinetic stabilizer drugs to transthyretin in plasma.

  DOI：

  10.1021/ja104999v

文献信息

• SMALL MOLECULES THAT COVALENTLY MODIFY TRANSTHYRETIN
  申请人：Kelly Jeffery W.

  公开号：US20120270938A1

  公开（公告）日：2012-10-25

  A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

  本文介绍了一类共价动力稳定剂化合物家族，它们选择性地、共价地与突出的血浆蛋白转甲状腺素结合，而不是其他4000多种人类血浆蛋白。一种可考虑的化合物对应于以下的结构式I，其中各取代基在内部定义，并与转甲状腺素四聚体中的一个或两个Lys-15 ε-氨基基团发生化学选择性反应。晶体结构证实了化合物亚结构和结合酰胺键的结合方向。与非共价对应物相比，共价转甲状腺素动力稳定剂表现出优越的淀粉样抑制效能，并抑制与淀粉样生成相关的细胞毒性。
• Small molecules that covalently modify transthyretin
  申请人：Kelly Jeffery W.

  公开号：US08703815B2

  公开（公告）日：2014-04-22

  A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

  本文披露了一类共价动力学稳定化合物家族，这些化合物具有选择性地与显著的血浆蛋白转甲状腺素共价反应，而不是与其他4000多种人类血浆蛋白反应。所考虑的化合物对应于下面的公式I的结构，其中各个取代基在内部被定义，并且与转甲状腺素四聚体中的四个Lys-15 ε-氨基基团之一或两个发生化学选择性反应。晶体结构证实了化合物亚结构和结合酰胺键的结合方向。共价转甲状腺素动力学稳定剂比非共价对应物具有更优异的淀粉样抑制效能，并抑制与淀粉样生成相关的细胞毒性。
• Small Molecules That Covalently Modify Transthyretin
  申请人：Kelly Jeffery W.

  公开号：US20140336254A1

  公开（公告）日：2014-11-13

  A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

  本发明揭示了一种共价动力稳定剂化合物家族，它们选择性地和共价地与显著的血浆蛋白转甲状腺素反应，而不是其他4000多种人类血浆蛋白。考虑到的化合物对应于以下公式I的结构，其中各种取代基在内部定义，并与转甲状腺素四聚体内的四个Lys-15 ε-氨基基团之一或两个发生化学选择性反应。晶体结构证实了化合物亚结构和结合酰胺键的结合方向。与非共价对应物相比，共价转甲状腺素动力稳定剂表现出优越的淀粉样抑制效力，并抑制与淀粉样生成相关的细胞毒性。
• US4002664A
  申请人：——

  公开号：US4002664A

  公开（公告）日：1977-01-11
• US8703815B2
  申请人：——

  公开号：US8703815B2

  公开（公告）日：2014-04-22