ethyl 4-(2-((tert-butoxycarbonylamino)methyl)morpholino)-3-(3-cyanophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate | 1034769-82-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-(2-((tert-butoxycarbonylamino)methyl)morpholino)-3-(3-cyanophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
• 英文别名: ethyl 3-(3-cyanophenyl)-4-[2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]morpholin-4-yl]-2H-pyrazolo[3,4-b]pyridine-5-carboxylate
• CAS: 1034769-82-8
• 化学式: C₂₆H₃₀N₆O₅
• 分子量: 506.561
• InChiKey: CMEBPYHXKYEZHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 4-(2-((tert-butoxycarbonylamino)methyl)morpholino)-3-(3-cyanophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 在 甲醇 、 三氟乙酸 、 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以62%的产率得到ethyl 4-(2-(aminomethyl)morpholino)-3-(3-cyanophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
  参考文献：
  名称：

  WO2008/75007

  摘要：

  公开号：
• 作为产物：
  描述：

  ethyl 4-(2-((tert-butoxycarbonylamino)methyl)morpholin-4-yl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 ethyl 4-(2-((tert-butoxycarbonylamino)methyl)morpholino)-3-(3-cyanophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
  参考文献：
  名称：

  Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

  摘要：

  Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.

  DOI：

  10.1021/jm2007326