4-amino-2-iodothieno[3,2-c]pyridine-7-carboxylic acid | 1350455-39-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 4-amino-2-iodothieno[3,2-c]pyridine-7-carboxylic acid
• CAS: 1350455-39-8
• 化学式: C₈H₅IN₂O₂S
• 分子量: 320.11
• InChiKey: NPDNCVVZWWTJJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-2-iodothieno[3,2-c]pyridine-7-carboxylic acid 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 4-amino-2-(4-(N-tert-butylsulfamoyl)phenyl)-N-(2-hydroxyethyl)-thieno[3,2-c]pyridine-7-carboxamide
  参考文献：
  名称：

  Discovery of Potent and Highly Selective Thienopyridine Janus Kinase 2 Inhibitors

  摘要：

  Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of a Jak2 gain-of-function mutation in the majority of patients with myeloproliferative disorders (MPD). Here, we describe the discovery of a thienopyridine series of Jak2 inhibitors that culminates with compounds showing 100- to >500-fold selectivity over the related Jak family kinases in enzyme assays. Selectivity for Jak2 was also observed in TEL-Jak cellular assays, as well as in cytokine-stimulated peripheral blood mononuclear cell (PBMC) and whole blood assays. X-ray cocrystal structures of 8 and 19 bound to the Jak2 kinase domain aided structure activity relationship efforts and, along with a previously reported small molecule X-ray cocrystal structure of the Jak1 kinase domain, provided structural rationale for the observed high levels of Jak2 selectivity.

  DOI：

  10.1021/jm200911r
• 作为产物：
  描述：

  2-iodo-4-(4-methoxybenzylamino)-thieno[3,2-c]pyridine-7-carbonitrile 在 盐酸 、 水 作用下， 以 二甲基亚砜 为溶剂， 以84%的产率得到4-amino-2-iodothieno[3,2-c]pyridine-7-carboxylic acid
  参考文献：
  名称：

  Discovery of Potent and Highly Selective Thienopyridine Janus Kinase 2 Inhibitors

  摘要：

  Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of a Jak2 gain-of-function mutation in the majority of patients with myeloproliferative disorders (MPD). Here, we describe the discovery of a thienopyridine series of Jak2 inhibitors that culminates with compounds showing 100- to >500-fold selectivity over the related Jak family kinases in enzyme assays. Selectivity for Jak2 was also observed in TEL-Jak cellular assays, as well as in cytokine-stimulated peripheral blood mononuclear cell (PBMC) and whole blood assays. X-ray cocrystal structures of 8 and 19 bound to the Jak2 kinase domain aided structure activity relationship efforts and, along with a previously reported small molecule X-ray cocrystal structure of the Jak1 kinase domain, provided structural rationale for the observed high levels of Jak2 selectivity.

  DOI：

  10.1021/jm200911r