4-chloro-6-ethyl-2-methyl-7H-pyrrolo[2,3-d]pyrimidine | 253332-23-9

• 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-7H-pyrrolo[2,3-d]pyrimidine
• CAS: 253332-23-9
• 化学式: C₉H₁₀ClN₃
• 分子量: 195.651
• InChiKey: WPSZGBCZDALODF-UHFFFAOYSA-N

物化性质

• 沸点：
  310.7±52.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-6-ethyl-2-methyl-7H-pyrrolo[2,3-d]pyrimidine 在 N-溴代丁二酰亚胺(NBS) 、 lithium chloro-isopropyl-magnesium chloride 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.17h， 生成 4-chloro-6-ethyl-2-methyl-7-(trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid
  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：

  1,7-dihydro-2-methyl-6-ethyl-4H-pyrrolo[2,3-d]pyrimidin-4-one 、 三氯氧磷 在 二氯甲烷 、 ice 、 potassium carbonate 、 水 、 brown residue 、 silica 、 methanol-dichloromethane 作用下， 反应 4.0h， 以to provide 3.32 g (86%) of 2-methyl-4-chloro-6-ethyl-1H-pyrrolo[2,3-d]pyrimidine as an off-white solid的产率得到4-chloro-6-ethyl-2-methyl-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Bicyclic sPLA2 inhibitors

  摘要：

  这些化合物属于吡咯并[2,3-d]嘧啶类，可用于抑制sPLA2介导的脂肪酸释放，用于治疗诸如感染性休克等疾病。

  公开号：

  US06384041B1

文献信息

• BICYCLIC sPLA 2 INHIBITORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1091738B1

  公开（公告）日：2006-12-06
• US6384041B1
  申请人：——

  公开号：US6384041B1

  公开（公告）日：2002-05-07
• Bicyclic sPLA2 inhibitors
  申请人：Eli Lilly and Company

  公开号：US06384041B1

  公开（公告）日：2002-05-07

  The compounds are of the class of pyrrolo[2,3-d]pyrimidines useful for inhibiting sPLA2 mediated release of fatty acids for treatment of diseases such as septic shock.

  这些化合物属于吡咯并[2,3-d]嘧啶类，可用于抑制sPLA2介导的脂肪酸释放，用于治疗诸如感染性休克等疾病。
• 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.