5-(苄氧基)-24-二氯苯硼酸 | 1256346-47-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-(苄氧基)-24-二氯苯硼酸
• 中文别名: 5-(苄氧基)-2,4-二氯苯基硼酸
• 英文名称: (5-(Benzyloxy)-2,4-dichlorophenyl)boronic acid
• 英文别名: (2,4-dichloro-5-phenylmethoxyphenyl)boronic acid
• CAS: 1256346-47-0
• 化学式: C₁₃H₁₁BCl₂O₃
• 分子量: 296.946
• InChiKey: WKVMHOHDMRUZMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氨基-4,6-二氯嘧啶 、 5-(苄氧基)-24-二氯苯硼酸 在 phosphate potassium salt 、 二(三叔丁基膦)钯 作用下， 以 甲醇 、 乙醇 、 水 、 甲苯 为溶剂， 反应 3.0h， 生成 4-(5-benzyloxy-2,4-dichlorophenyl)-6-chloropyrimidin-2-ylamine
  参考文献：
  名称：

  Fragment-Based Drug Discovery Applied to Hsp90. Discovery of Two Lead Series with High Ligand Efficiency

  摘要：

  Inhibitors of the chaperone Hsp90 are potentially useful as chemotherapeutic agents in cancer. This paper describes an application of fragment screening to Hsp90 using a combination of NMR and high throughput X-ray crystallography. The screening identified an aminopyrimidine with affinity in the high micromolar range and subsequent structure-based design allowed its optimization into a low nanomolar series with good ligand efficiency. A phenolic chemotype was also identified in fragment screening and was found to bind with affinity close to 1 mM. This fragment was optimized using structure based design into a resorcinol lead which has subnanomolar affinity for Hsp90, excellent cell potency, and good ligand efficiency. This fragment to lead campaign improved affinity for Hsp90 by over 1,000,000-fold with the addition of only six heavy atoms. The companion paper (DOI: 10.1021/jm100060b) describes how the resorcinol lead was optimized into a compound that is now in clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm100059d
• 作为产物：
  描述：

  1-苄氧基-2,4-二氯-5-碘苯 在 正丁基锂 、 硼酸三异丙酯 作用下， 以 四氢呋喃 为溶剂， 生成 5-(苄氧基)-24-二氯苯硼酸
  参考文献：
  名称：

  Fragment-Based Drug Discovery Applied to Hsp90. Discovery of Two Lead Series with High Ligand Efficiency

  摘要：

  Inhibitors of the chaperone Hsp90 are potentially useful as chemotherapeutic agents in cancer. This paper describes an application of fragment screening to Hsp90 using a combination of NMR and high throughput X-ray crystallography. The screening identified an aminopyrimidine with affinity in the high micromolar range and subsequent structure-based design allowed its optimization into a low nanomolar series with good ligand efficiency. A phenolic chemotype was also identified in fragment screening and was found to bind with affinity close to 1 mM. This fragment was optimized using structure based design into a resorcinol lead which has subnanomolar affinity for Hsp90, excellent cell potency, and good ligand efficiency. This fragment to lead campaign improved affinity for Hsp90 by over 1,000,000-fold with the addition of only six heavy atoms. The companion paper (DOI: 10.1021/jm100060b) describes how the resorcinol lead was optimized into a compound that is now in clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm100059d

文献信息

• Pyrimidine Derivatives As HSP90 Inhibitors
  申请人：Chessari Gianni

  公开号：US20090215777A1

  公开（公告）日：2009-08-27

  The invention provides a compound for use as an inhibitor of Hsp90, the compound having the formula (I): or salts, tautomers, solvates or N-oxides thereof; wherein: A is N or a group CR 3 ; R 1 is a monocyclic or bicyclic carbocyclic or heterocyclic ring of 5 to 10 ring members of which up to two ring members may be heteroatoms selected from N, O and S and the remainder are carbon atoms, the carbocyclic or heterocyclic ring being optionally substituted by one or more substituent groups independently selected from R 10 ; and R 2 , R 3 and R 10 are as defined in the claims.

  该发明提供了一种化合物，用作Hsp90的抑制剂，该化合物具有以下式（I）：或其盐、互变异构体、溶剂合物或N-氧化物；其中：A为N或CR基团；R1为由5至10个环成员组成的单环或双环碳环或杂环，其中最多两个环成员可以是从N、O和S中选择的杂原子，其余为碳原子，碳环或杂环可以选择地被一个或多个取代基独立地选择自R10的取代基取代；而R2、R3和R10如权利要求中所定义。
• Fragment-Based Drug Discovery Applied to Hsp90. Discovery of Two Lead Series with High Ligand Efficiency
  作者：Christopher W. Murray、Maria G. Carr、Owen Callaghan、Gianni Chessari、Miles Congreve、Suzanna Cowan、Joseph E. Coyle、Robert Downham、Eva Figueroa、Martyn Frederickson、Brent Graham、Rachel McMenamin、M. Alistair O’Brien、Sahil Patel、Theresa R. Phillips、Glyn Williams、Andrew J. Woodhead、Alison J.-A. Woolford

  DOI：10.1021/jm100059d

  日期：2010.8.26

  Inhibitors of the chaperone Hsp90 are potentially useful as chemotherapeutic agents in cancer. This paper describes an application of fragment screening to Hsp90 using a combination of NMR and high throughput X-ray crystallography. The screening identified an aminopyrimidine with affinity in the high micromolar range and subsequent structure-based design allowed its optimization into a low nanomolar series with good ligand efficiency. A phenolic chemotype was also identified in fragment screening and was found to bind with affinity close to 1 mM. This fragment was optimized using structure based design into a resorcinol lead which has subnanomolar affinity for Hsp90, excellent cell potency, and good ligand efficiency. This fragment to lead campaign improved affinity for Hsp90 by over 1,000,000-fold with the addition of only six heavy atoms. The companion paper (DOI: 10.1021/jm100060b) describes how the resorcinol lead was optimized into a compound that is now in clinical trials for the treatment of cancer.