8-(2-chloro-3,4,5-trimethoxy-benzyl)-2-chloro-9H-purin-6-ylamine | 511253-83-1

• 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: 8-(2-chloro-3,4,5-trimethoxy-benzyl)-2-chloro-9H-purin-6-ylamine
• 英文别名: 8-[(2-chloro-3,4,5-trimethoxyphenyl)methyl]-2-fluoro-7H-purin-6-amine
• CAS: 511253-83-1
• 化学式: C₁₅H₁₅ClFN₅O₃
• 分子量: 367.767
• InChiKey: QRMZXZGIAOWVTK-UHFFFAOYSA-N

物化性质

• 沸点：
  675.6±65.0 °C(Predicted)
• 密度：
  1.462±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  25.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  108.17
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-戊炔-1-醇 、 8-(2-chloro-3,4,5-trimethoxy-benzyl)-2-chloro-9H-purin-6-ylamine 在 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 以76%的产率得到8-(2-chloro-3,4,5-trimethoxy-benzyl)-2-fluoro-9-pent-4-ynyl-9H-purin-6-ylamine
  参考文献：
  名称：

  Development of a Purine-Scaffold Novel Class of Hsp90 Binders that Inhibit the Proliferation of Cancer Cells and Induce the Degradation of Her2 Tyrosine Kinase

  摘要：

  The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71) exhibits binding to hsp90 comparable to the natural product derivative 17AAG that is now in Phase I clinical trial as a cancer therapeutic. 71 Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50 = 2 muM). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00253-5
• 作为产物：
  描述：

  8-(3,4,5-trimethoxy-benzyl)-9H-purine-2,6-diamine 在 吡啶 、 盐酸 、 叔丁基过氧化氢 、 亚硝酸特丁酯 、 氢氟酸 作用下， 以 甲醇 、 水 为溶剂， 反应 20.5h， 生成 8-(2-chloro-3,4,5-trimethoxy-benzyl)-2-chloro-9H-purin-6-ylamine
  参考文献：
  名称：

  Development of a Purine-Scaffold Novel Class of Hsp90 Binders that Inhibit the Proliferation of Cancer Cells and Induce the Degradation of Her2 Tyrosine Kinase

  摘要：

  The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71) exhibits binding to hsp90 comparable to the natural product derivative 17AAG that is now in Phase I clinical trial as a cancer therapeutic. 71 Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50 = 2 muM). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00253-5

文献信息

• Adenine derived inhibitors of the molecular chaperone HSP90—SAR explained through multiple X-ray structures
  作者：Brian Dymock、Xavier Barril、Mandy Beswick、Adam Collier、Nicholas Davies、Martin Drysdale、Alexandra Fink、Christophe Fromont、Roderick E. Hubbard、Andrew Massey、Allan Surgenor、Lisa Wright

  DOI：10.1016/j.bmcl.2003.11.011

  日期：2004.1

  Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.