N-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-YL)cyclopropanecarboxamide | 1201644-41-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-YL)cyclopropanecarboxamide
• 英文别名: N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]cyclopropanecarboxamide
• CAS: 1201644-41-8
• 化学式: C₁₅H₂₁BN₂O₃
• 分子量: 288.154
• InChiKey: ZRPVYUGIEIMFBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.73
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl N-(4-bromo-2-fluorophenyl)-N-[({4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl} carbamoyl)methyl]-carbamate 、 N-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-YL)cyclopropanecarboxamide 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 生成 tert-butyl (4-(6-(cyclopropanecarboxamido)pyridin-3-yl)-2-fluorophenyl)(2-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)amino)-2-oxoethyl)carbamate
  参考文献：
  名称：

  Structure–Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells

  摘要：

  Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2. Initial structure activity relationship studies resulted in compound 27 with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors 53 and 54, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented.

  DOI：

  10.1021/acs.jmedchem.5b01712