[4-[[7-Cyclopentyl-6-(methylaminomethyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1-methylpyrrol-2-yl]-(4-methylpiperazin-1-yl)methanone | 1383481-50-2

• 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: [4-[[7-Cyclopentyl-6-(methylaminomethyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1-methylpyrrol-2-yl]-(4-methylpiperazin-1-yl)methanone
• CAS: 1383481-50-2
• 化学式: C₂₄H₃₄N₈O
• 分子量: 450.587
• InChiKey: VCLDLBGMMXCQJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  83.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 4-((7-cyclopentyl-6-(diethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-1-methyl-1H-pyrrole-2-carboxylate 在 盐酸 、 甲醇 、 水 、 sodium cyanoborohydride 、 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-) 、 potassium hydroxide 作用下， 以 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 [4-[[7-Cyclopentyl-6-(methylaminomethyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1-methylpyrrol-2-yl]-(4-methylpiperazin-1-yl)methanone
  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

文献信息

• Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as Aurora kinases inhibitors
  作者：Jean-Yves Le Brazidec、Angela Pasis、Betty Tam、Christina Boykin、Deping Wang、Douglas J. Marcotte、Gisela Claassen、Jer-Hong Chong、Jianhua Chao、Junhua Fan、Khanh Nguyen、Laura Silvian、Leona Ling、Lin Zhang、Michael Choi、Min Teng、Nuzhat Pathan、Shuo Zhao、Tony Li、Art Taveras

  DOI：10.1016/j.bmcl.2012.04.085

  日期：2012.6

  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.