4-amino-2-(4-(N-tert-butylsulfamoyl)phenyl)thieno[3,2-c]-pyridine-7-carboxylic Acid | 1350455-41-2

• 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: 4-amino-2-(4-(N-tert-butylsulfamoyl)phenyl)thieno[3,2-c]-pyridine-7-carboxylic Acid
• CAS: 1350455-41-2
• 化学式: C₁₈H₁₉N₃O₄S₂
• 分子量: 405.499
• InChiKey: GGXVTQGUYFAPCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  122.38
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 4-amino-2-(4-(N-tert-butylsulfamoyl)phenyl)thieno[3,2-c]-pyridine-7-carboxylic Acid 在 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 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以30%的产率得到4-amino-2-(4-(N-tert-butylsulfamoyl)phenyl)-N-(3-morpholinopropyl)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 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 4-amino-2-(4-(N-tert-butylsulfamoyl)phenyl)thieno[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