甲基3-氨基-5-(3-硝基苯基)-2-噻吩羧酸酯 | 474843-42-0

• 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: 甲基3-氨基-5-(3-硝基苯基)-2-噻吩羧酸酯
• 英文名称: 3-amino-5-(3-nitrophenyl)thiophene-2-carboxylic acid methyl ester
• 英文别名: Methyl 3-amino-5-(3-nitrophenyl)thiophene-2-carboxylate
• CAS: 474843-42-0
• 化学式: C₁₂H₁₀N₂O₄S
• 分子量: 278.288
• InChiKey: JEUDVSQLUHEQMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  甲基3-氨基-5-(3-硝基苯基)-2-噻吩羧酸酯 在 palladium on activated charcoal sodium hydroxide 、 TEA 、 水 、 氢气 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 64.0h， 生成 5-(3-Amino-phenyl)-3-(oxalyl-amino)-thiophene-2-carboxylic acid
  参考文献：
  名称：

  Discovery and SAR of a Novel Selective and Orally Bioavailable Nonpeptide Classical Competitive Inhibitor Class of Protein-Tyrosine Phosphatase 1B

  摘要：

  Reversible phosphorylation and dephosphorylation of key proteins on tyrosine residues are important parts of intracellular signaling triggered by hormones and other agents. Recent knock-out studies in mice have identified PTP1B as a potential target for the treatment of diabetes and obesity. As a consequence, a number of academic and industrial groups are aggressively pursuing the development of selective PTP1B inhibitors. In addition, other protein-tyrosine phosphatases (PTPs) appear to be critically involved in major diseases such as cancer and autoimmunity. Given the diversity of PTPs and their potential as drug targets in different diseases, we have taken a broad approach to develop active site-directed selective inhibitors of specific members of this family of enzymes. Using a high throughput screening, we have previously identified 2-(oxalylamino)benzoic acid 3a as a relatively weak but classical competitive inhibitor of several PTPs.(4) On the basis of our early studies, indicating that 3a might be used as a starting point for the synthesis of selective PTP inhibitors, we now present our efforts in expansion of this concept and provide here a number of new chemical scaffolds for the development of inhibitors of different members of the PTP family. Although the core structure of these inhibitors is charged, good oral bioavailability has been observed in rat for some compounds. Furthermore, we have observed enhancement of 2-deoxy-glucose accumulation in C2C12 cells with prodrug analogues.

  DOI：

  10.1021/jm0209026
• 作为产物：
  描述：

  间硝基苯乙酮 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 甲基3-氨基-5-(3-硝基苯基)-2-噻吩羧酸酯
  参考文献：
  名称：

  Structure-Guided Optimization of Small-Molecule Folate Uptake Inhibitors Targeting the Energy-Coupling Factor Transporters

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c02114

文献信息

• Novel small molecule inhibitors targeting the “switch region” of bacterial RNAP: Structure-based optimization of a virtual screening hit
  作者：J. Henning Sahner、Matthias Groh、Matthias Negri、Jörg Haupenthal、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2013.04.060

  日期：2013.7

  Rising resistance against current antibiotics necessitates the development of antibacterial agents with alternative targets. The "switch region" of RNA polymerase (RNAP), addressed by the myxopyronins, could be such a novel target site. Based on a hit candidate discovered by virtual screening, a small library of 5-phenyl-3-ureidothiophene-2-carboxylic acids was synthesized resulting in compounds with increased RNAP inhibition. Hansch analysis revealed pi (lipophilicity constant) and sigma (Hammet substituent constant) of the substituents at the 5-phenyl moiety to be crucial for activity. The binding mode was proven by the targeted introduction of a moiety mimicking the enecarbamate side chain of myxopyronin into the hit compound, accompanied by enhanced RNAP inhibitory potency. The new compounds displayed good antibacterial activities against Gram positive bacteria and Gram negative Escherichia coli TolC and a reduced resistance frequency compared to the established antibiotic rifampicin. (C) 2013 Elsevier Masson SAS. All rights reserved.