2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)amide | 1185428-40-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 英文名称: 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)amide
• 英文别名: 2-cyclopropyl-N-[(2S)-3-hydroxy-3-methylbutan-2-yl]-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazine-7-carboxamide
• CAS: 1185428-40-3
• 化学式: C₂₁H₃₄N₄O₃Si
• 分子量: 418.611
• InChiKey: PMASSCMVZWPKFY-AWEZNQCLSA-N

物化性质

• 沸点：
  598.7±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  89.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)amide 在 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.5h， 生成 2-Cyclopropyl-N-[(2s)-3-Hydroxy-3-Methylbutan-2-Yl]-5h-Pyrrolo[2,3-B]pyrazine-7-Carboxamide
  参考文献：
  名称：

  3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models

  摘要：

  The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.

  DOI：

  10.1021/jm301646k
• 作为产物：
  描述：

  (2-溴-5H-吡咯并[2,3-B]吡嗪-7-基)甲醇 在 4-二甲氨基吡啶 、 sodium chlorite 、 potassium phosphate 、 potassium dihydrogenphosphate 、 Jones reagent 、 氨基磺酸 、 palladium diacetate 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三环己基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 24.5h， 生成 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)amide
  参考文献：
  名称：

  3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models

  摘要：

  The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.

  DOI：

  10.1021/jm301646k

文献信息

• 3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models
  作者：Michael Soth、Johannes C. Hermann、Calvin Yee、Muzaffar Alam、Jim W. Barnett、Pamela Berry、Michelle F. Browner、Karl Frank、Sandra Frauchiger、Seth Harris、Yang He、Mohammad Hekmat-Nejad、Than Hendricks、Robert Henningsen、Ramona Hilgenkamp、Hoangdung Ho、Ann Hoffman、Pei-Yuan Hsu、Dong-Qing Hu、Andrea Itano、Saul Jaime-Figueroa、Alam Jahangir、Sue Jin、Andreas Kuglstatter、Alan K. Kutach、Cheng Liao、Stephen Lynch、John Menke、Linghao Niu、Vaishali Patel、Aruna Railkar、Douglas Roy、Ada Shao、David Shaw、Sandra Steiner、Yongliang Sun、Seng-Lai Tan、Sandra Wang、Minh Diem Vu

  DOI：10.1021/jm301646k

  日期：2013.1.10

  The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.