5-(3-aminophenyl)-4-bromo-3-tert-butoxycarbonylmethoxythiophene-2-carboxylic acid methyl ester | 864132-41-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-(3-aminophenyl)-4-bromo-3-tert-butoxycarbonylmethoxythiophene-2-carboxylic acid methyl ester
• 英文别名: Methyl 5-(3-aminophenyl)-4-bromo-3-(2-(tert-butoxy)-2-oxoethoxy)thiophene-2-carboxylate；methyl 5-(3-aminophenyl)-4-bromo-3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]thiophene-2-carboxylate
• CAS: 864132-41-2
• 化学式: C₁₈H₂₀BrNO₅S
• 分子量: 442.331
• InChiKey: NMGRRBGPKKJGMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(3-aminophenyl)-4-bromo-3-tert-butoxycarbonylmethoxythiophene-2-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以71%的产率得到5-(3-amino-phenyl)-4-bromo-3-carboxymethoxy-thiophene-2-carboxylic acid
  参考文献：
  名称：

  基于结构的蛋白质酪氨酸磷酸酶1B抑制剂的优化：从活性位点到第二个磷酸酪氨酸结合位点。

  摘要：

  蛋白酪氨酸磷酸酶1B（PTP1B）是胰岛素和瘦素受体途径的负调节剂，因此是糖尿病和肥胖症的有吸引力的治疗靶标。从高微摩尔的先导化合物开始，描述了通过将分子从酶活性位点延伸到第二个磷酸酪氨酸结合位点来对新型PTP1B抑制剂进行基于结构的优化。在X射线复合物结构和分子建模的指导下，药物化学已经以有效的方式产生了低纳摩尔PTP1B抑制剂。发现来自该化学系列的化合物被主动转运到肝细胞中。这种对靶组织的主动摄取可能是克服PTP1B抑制剂膜通透性差的可能途径之一。

  DOI：

  10.1021/jm0702478
• 作为产物：
  描述：

  4,5-dibromo-3-tert-butoxycarbonylmethoxythiophene-2-carboxylic acid methyl ester 、 3-氨基苯硼酸 在 四(三苯基膦)钯 potassium fluoride 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以70%的产率得到5-(3-aminophenyl)-4-bromo-3-tert-butoxycarbonylmethoxythiophene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  基于结构的蛋白质酪氨酸磷酸酶1B抑制剂的优化：从活性位点到第二个磷酸酪氨酸结合位点。

  摘要：

  蛋白酪氨酸磷酸酶1B（PTP1B）是胰岛素和瘦素受体途径的负调节剂，因此是糖尿病和肥胖症的有吸引力的治疗靶标。从高微摩尔的先导化合物开始，描述了通过将分子从酶活性位点延伸到第二个磷酸酪氨酸结合位点来对新型PTP1B抑制剂进行基于结构的优化。在X射线复合物结构和分子建模的指导下，药物化学已经以有效的方式产生了低纳摩尔PTP1B抑制剂。发现来自该化学系列的化合物被主动转运到肝细胞中。这种对靶组织的主动摄取可能是克服PTP1B抑制剂膜通透性差的可能途径之一。

  DOI：

  10.1021/jm0702478

文献信息

• Inhibitors of protein tyrosine phosphatase 1B
  申请人：Lee Jinbo

  公开号：US20050203087A1

  公开（公告）日：2005-09-15

  Protein tyrosine phosphatases (PTPases) such as PTP1B can play a role in regulating a wide variety of cellular responses such as insulin signaling. Substituted thiophene compounds such as, for example, 2-carboxyl, 3-carboxymethoxy, 5-aryl substituted thiophenes, can inhibit PTP1B and thereby induce greater insulin sensitivity. Accordingly, PTP1B inhibition can provide an alternate treatment for PTPase-mediated disorders such as diabetes.

  蛋白酪氨酸磷酸酶（PTPases）如PTP1B可以在调节多种细胞反应中发挥作用，例如胰岛素信号传导。取代噻吩化合物，例如2-羧基、3-羧甲氧基、5-芳基取代的噻吩，可以抑制PTP1B，从而增加胰岛素敏感性。因此，PTP1B抑制可以作为PTPase介导的疾病（如糖尿病）的替代治疗方法。
• METHOD FOR CELL MEMBRANE PERMEATION FOR COMPOUND
  申请人：HitGen LTD.

  公开号：US20160153002A1

  公开（公告）日：2016-06-02

  The present invention discloses a cell-penetrating method for compounds, comprising the following steps of: (1) preparing raw materials, i.e., the compounds and DNA or RNA; (2) linking: linking the compounds to the DNA or RNA to obtain a molecular conjugate; and (3) transferring: transferring the molecular conjugate obtained in the step (2) into cells by a gene transfer method. The present invention further discloses a structure of a molecular conjugate for transmembrane transfer and a method for synthesizing the molecular conjugate. The method of the present invention effectively solves a problem of low membrane permeability of compounds, so that the compounds enter the cell to act on targets thereof, thus to provide a novel drug-delivery way. The method of the present invention may be used for clinical treatment by drugs with low membrane permeability. This method significantly increases the quantity of potential drugs, and the clinical application of many drugs which are eliminated due to their low membrane permeability becomes possible. The method of the present invention may be used for capturing unknown targets of drugs in cells and conducting researches on the target mechanism. This method significantly shortens the course of research and development of drugs and has excellent application prospect.

  本发明公开了一种化合物的细胞穿透方法，包括以下步骤：(1)准备原材料，即化合物和DNA或RNA；(2)连接：将化合物连接到DNA或RNA以获得分子共轭物；和(3)转移：通过基因转移方法将在步骤(2)中获得的分子共轭物转移到细胞中。本发明还公开了一种用于跨膜转移的分子共轭物的结构和合成该分子共轭物的方法。本发明的方法有效解决了化合物低膜通透性的问题，使化合物进入细胞作用于其靶标，从而提供了一种新的药物传递方式。本发明的方法可用于具有低膜通透性的药物的临床治疗。该方法显著增加了潜在药物的数量，并使许多因其低膜通透性而被淘汰的药物的临床应用成为可能。本发明的方法可用于在细胞中捕获药物的未知靶标并对靶标机制进行研究。该方法显著缩短了药物研发过程，并具有极佳的应用前景。
• COMPOUND ADMINISTRATION PRECURSOR AND MEDICAMENT CARRIER PREPARATION
  申请人：HitGen LTD.

  公开号：US20160152976A1

  公开（公告）日：2016-06-02

  The present invention provides a compound drug-delivery precursor for membrane permeation, and a drug carrier preparation based on this precursor. The compound drug-delivery precursor and the drug carrier preparation of the present invention may effectively improve the membrane permeability of compounds with low membrane permeability and provide a new choice for clinical medication.

  本发明提供了一种用于膜渗透的化合物药物传递前体，以及基于该前体的药物载体制备。本发明的化合物药物传递前体和药物载体制备可以有效提高膜透性低的化合物的膜透性，并为临床用药提供了新选择。
• DRUG TARGET CAPTURING METHOD
  申请人：HitGen LTD.

  公开号：US20160154013A1

  公开（公告）日：2016-06-02

  The present invention discloses a method for capturing drug targets, comprising the following steps of: (1) preparing row materials, i.e., compounds and DNA or RNA or one party of other specific affinity materials; (2) linking: covalently linking the compounds to the DNA or RNA or the one party of other specific affinity materials, to obtain labeled compounds; (3) transferring: transferring the labeled compounds obtained in the step (2) into cells by a specific gene transfer method; (4) capturing targets: disrupting the cells in the step (3), and then capturing the DNA or RNA in the step (1) by immobilized complementary DNA or RNA, or capturing the one party of affinity materials in the step (1) by the other party of immobilized specific affinity materials, thus to enrich the targets through the covalently linked labeled compounds and the affinity of the targets; (5) identifying targets: dissociating the enriched targets from a stationary phase, deploying the targets by a gel electrophoresis method or by an equivalent separation method, and comparing differential proteins by proteomics thus to identify the potential targets; and (6) determining targets: expressing or purchasing the targets identified in the step (5) by priority, and comparing by interaction of the compounds with those targets one by one to determine the targets for the compounds. By the method of the present invention, compounds with low membrane permeability may be transferred into cells to be bound with the targets in the cells, to realize the target identification closer to the real physiological environment and thus provide more conclusive evidences for the acting mechanism of the compounds to diseases. Additionally, the method for capturing drug targets of the present invention is novel, easy, efficient, and low in cost, and has good application prospects.

  本发明公开了一种药物靶点捕获方法，包括以下步骤：（1）准备原料，即化合物和DNA或RNA或其他特定亲和材料之一；（2）连接：将化合物与DNA或RNA或其他特定亲和材料之一共价连接，获得标记化合物；（3）转移：通过特定的基因转移方法将步骤（2）中获得的标记化合物转移到细胞中；（4）捕获靶点：破坏步骤（3）中的细胞，然后通过固定的互补DNA或RNA捕获步骤（1）中的DNA或RNA，或通过固定的其他特定亲和材料捕获步骤（1）中的亲和材料，从而通过共价连接的标记化合物和靶点的亲和力富集靶点；（5）鉴定靶点：将富集的靶点从固定相中解离，通过凝胶电泳方法或等效分离方法展开靶点，并通过蛋白质组学比较差异蛋白质，从而识别潜在的靶点；（6）确定靶点：按优先顺序表达或购买步骤（5）中识别的靶点，并逐一与这些靶点相互作用进行比较，以确定化合物的靶点。通过本发明的方法，低透膜性的化合物可以转移到细胞中与细胞内的靶点结合，实现更接近真实生理环境的靶点鉴定，从而为化合物对疾病的作用机制提供更有力的证据。此外，本发明的药物靶点捕获方法新颖、简便、高效、成本低，具有良好的应用前景。
• US7521473B2
  申请人：——

  公开号：US7521473B2

  公开（公告）日：2009-04-21