4-chloro-6-ethyl-2-methyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine | 1314782-34-7

• 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-chloro-6-ethyl-2-methyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine
• CAS: 1314782-34-7
• 化学式: C₁₅H₂₄ClN₃OSi
• 分子量: 325.914
• InChiKey: GREYSGRETLUUMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.27
• 重原子数：
  21.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  39.94
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-chloro-6-ethyl-2-methyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine 在 N-溴代丁二酰亚胺(NBS) 、 lithium chloro-isopropyl-magnesium chloride 、 草酰氯 、 氨 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.09h， 生成 4-chloro-6-ethyl-2-methyl-7-(trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid amide
  参考文献：
  名称：

  Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone

  摘要：

  A series of novel and potent small molecule Hsp90 inhibitors was optimized using X-ray crystal structures. These compounds bind in a deep pocket of the Hsp90 enzyme that is partially comprised by residues Asn51 and Ser52. Displacement of several water molecules observed crystallographically in this pocket using rule-based strategies led to significant improvements in inhibitor potency. An optimized inhibitor (compound 17) exhibited potent Hsp90 inhibition in ITC, biochemical, and cell-based assays (K-d = 1.3 nM, K-i = 15 nM, and cellular IC50 = 0.5 mu M). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.130
• 作为产物：
  描述：

  4-chloro-6-ethyl-2-methyl-7H-pyrrolo[2,3-d]pyrimidine 、 2-(三甲基硅烷基)乙氧甲基氯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以87%的产率得到4-chloro-6-ethyl-2-methyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone

  摘要：

  A series of novel and potent small molecule Hsp90 inhibitors was optimized using X-ray crystal structures. These compounds bind in a deep pocket of the Hsp90 enzyme that is partially comprised by residues Asn51 and Ser52. Displacement of several water molecules observed crystallographically in this pocket using rule-based strategies led to significant improvements in inhibitor potency. An optimized inhibitor (compound 17) exhibited potent Hsp90 inhibition in ITC, biochemical, and cell-based assays (K-d = 1.3 nM, K-i = 15 nM, and cellular IC50 = 0.5 mu M). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.130