3-((3-aminophenyl)ethynyl)-1-isopropyl-1H-pyrazolo[3,4-d]-pyrimidin-4-amine | 1378287-83-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 3-((3-aminophenyl)ethynyl)-1-isopropyl-1H-pyrazolo[3,4-d]-pyrimidin-4-amine
• 英文别名: 3-((3-aminophenyl)ethynyl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine；3-[2-(3-Aminophenyl)ethynyl]-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 1378287-83-2
• 化学式: C₁₆H₁₆N₆
• 分子量: 292.343
• InChiKey: XYHJHIRTHHPPSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  95.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-((3-aminophenyl)ethynyl)-1-isopropyl-1H-pyrazolo[3,4-d]-pyrimidin-4-amine 、 2-三氟甲基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以49%的产率得到N-(3-((4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-ethynyl)phenyl)-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Development of Alkyne-Containing Pyrazolopyrimidines To Overcome Drug Resistance of Bcr-Abl Kinase

  摘要：

  Despite the success of imatinib at inhibiting Bcr-Abl and treating chronic myelogenous leukemia (CML), resistance to the therapy occurs over time in patients. In particular, the resistance to imatinib caused by the gatekeeper mutation T315I in Bcr-Abl remains a challenge in the clinic. Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-Abl(T315I) by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. Herein, we describe the design, synthesis, and characterization of a series of alkyne-containing pyrazolopyrimidines as Bcr-Abl inhibitors. Our results demonstrate that some alkyne-containing pyrazolopyrimidines potently inhibit not only Abl(T315I) in vitro but also Bcr-Abl(T315I) in cells. These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted therapy to overcome drug resistance of CML.

  DOI：

  10.1021/acs.jmedchem.5b01125
• 作为产物：
  描述：

  4-氨基吡唑并[3,4-d]嘧啶 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.33h， 生成 3-((3-aminophenyl)ethynyl)-1-isopropyl-1H-pyrazolo[3,4-d]-pyrimidin-4-amine
  参考文献：
  名称：

  Preparation of 3-Substituted-1-Isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines as RET Kinase Inhibitors

  摘要：

  A series of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines have been designed, synthesized, and evaluated as RET protein kinase inhibitors. On the basis of docking results, a small library of pyrazolopyrimidine compounds with an extended hydrophobic side arm was synthesized. The most promising of the compounds (7a) displayed efficient inhibition in vitro and good selectivity when tested on a panel of kinases. Furthermore, 7a inhibited GDNF-induced RET phosphorylation of ERK1/2 in MCF-7 breast cancer cells at concentrations as low as 100 nM.

  DOI：

  10.1021/jm3003944