4-(2,4-dichloro-5-methoxyphenyl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile | 1314782-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(2,4-dichloro-5-methoxyphenyl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 1314782-25-6
• 化学式: C₁₅H₁₀Cl₂N₄O
• 分子量: 333.177
• InChiKey: XQAFNWQVIXKAPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  74.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氯-2-甲基-1H-吡咯并[2,3-d]嘧啶 在 四(三苯基膦)钯 、 碘 、 sodium carbonate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 4-(2,4-dichloro-5-methoxyphenyl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
  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

文献信息

• Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone
  作者：Pei-Pei Kung、Piet-Jan Sinnema、Paul Richardson、Michael J. Hickey、Ketan S. Gajiwala、Fen Wang、Buwen Huang、Guy McClellan、Jeff Wang、Karen Maegley、Simon Bergqvist、Pramod P. Mehta、Robert Kania

  DOI：10.1016/j.bmcl.2011.04.130

  日期：2011.6

  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.