7-cyclopentyl-2-((1-methyl-5-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde | 1383481-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 7-cyclopentyl-2-((1-methyl-5-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde
• CAS: 1383481-46-6
• 化学式: C₂₃H₂₉N₇O₂
• 分子量: 435.529
• InChiKey: QLLXIGYTPJBDNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.83
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  88.29
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  7-cyclopentyl-2-((1-methyl-5-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde 在 盐酸羟胺 、 sodium acetate 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 7-Cyclopentyl-2-[[1-methyl-5-(4-methylpiperazine-1-carbonyl)pyrrol-3-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carbonitrile
  参考文献：
  名称：

  Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as Aurora kinases inhibitors

  摘要：

  This Letter reports the optimization of a pyrrolopyrimidine series as dual inhibitors of Aurora A/B kinases. This series derived from a pyrazolopyrimidine series previously reported as inhibitors of aurora kinases and CDKs. In an effort to improve the selectivity of this chemotype, we switched to the pyrrolopyrimidine core which allowed functionalization on C-2. In addition, the modeling rationale was based on superimposing the structures of Aurora-A kinase and CDK2 which revealed enough differences leading to a path for selectivity improvement. The synthesis of the new series of pyrrolopyrimidine analogs relied on the development of a different route for the two key intermediates 7 and 19 which led to analogs with both tunable activity against CDK1 and maintained cell potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.085
• 作为产物：
  描述：

  5-溴-2-氯-N-环戊基-4-嘧啶胺 在 盐酸 、 甲醇 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 copper(l) iodide 、 四丁基氟化铵 、 水 、 palladium diacetate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 7-cyclopentyl-2-((1-methyl-5-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde
  参考文献：
  名称：

  Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as Aurora kinases inhibitors

  摘要：

  This Letter reports the optimization of a pyrrolopyrimidine series as dual inhibitors of Aurora A/B kinases. This series derived from a pyrazolopyrimidine series previously reported as inhibitors of aurora kinases and CDKs. In an effort to improve the selectivity of this chemotype, we switched to the pyrrolopyrimidine core which allowed functionalization on C-2. In addition, the modeling rationale was based on superimposing the structures of Aurora-A kinase and CDK2 which revealed enough differences leading to a path for selectivity improvement. The synthesis of the new series of pyrrolopyrimidine analogs relied on the development of a different route for the two key intermediates 7 and 19 which led to analogs with both tunable activity against CDK1 and maintained cell potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.085