2-(ethoxyoxalylamino)-6-pyridin-3-ylmethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid ethyl ester | 474844-03-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(ethoxyoxalylamino)-6-pyridin-3-ylmethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid ethyl ester
• 英文别名: ethyl 2-[(2-ethoxy-2-oxoacetyl)amino]-6-(pyridin-3-ylmethyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylate
• CAS: 474844-03-6
• 化学式: C₂₀H₂₃N₃O₅S
• 分子量: 417.486
• InChiKey: XDXOQICDDFBUAP-UHFFFAOYSA-N

物化性质

• 密度：
  1.336±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(ethoxyoxalylamino)-6-pyridin-3-ylmethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 16.0h， 生成 2-(hydroxyoxalyl-amino)-6-pyridin-4-ylmethyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-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：

  N-叔丁氧羰基-4-哌啶酮 在 吗啉 、 TEA 、 potassium carbonate 、 sulfur 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 50.5h， 生成 2-(ethoxyoxalylamino)-6-pyridin-3-ylmethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid ethyl ester
  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