3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyethoxy)benzaldehyde | 1429129-74-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyethoxy)benzaldehyde
• 英文别名: 3-(3,5-Dimethyl-1,2-oxazol-4-yl)-5-(2-methoxyethoxy)benzaldehyde；3-(3,5-dimethyl-1,2-oxazol-4-yl)-5-(2-methoxyethoxy)benzaldehyde
• CAS: 1429129-74-7
• 化学式: C₁₅H₁₇NO₄
• 分子量: 275.304
• InChiKey: MGIRUSXRUQHSDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyethoxy)benzaldehyde 、 苯基溴化镁 以 四氢呋喃 为溶剂， 反应 1.5h， 以83%的产率得到[3-(3,5-Dimethyl-1,2-oxazol-4-yl)-5-(2-methoxyethoxy)phenyl]-phenylmethanol
  参考文献：
  名称：

  Optimization of 3,5-Dimethylisoxazole Derivatives as Potent Bromodomain Ligands

  摘要：

  The bromodomain protein module, which binds to acetylated lysine, is emerging as an important epigenetic therapeutic target. We report the structure-guided optimization of 3,5-dimethylisoxazole derivatives to develop potent inhibitors of the BET (bromodomain and extra terminal domain) bromodomain family with good ligand efficiency. X-ray crystal structures of the most potent compounds reveal key interactions required for high affinity at BRD4(1). Cellular studies demonstrate that the phenol and acetate derivatives of the lead compounds showed strong antiproliferative effects on MV4;11 acute myeloid leukemia cells, as shown for other BET bromodomain inhibitors and genetic BRD4 knockdown, whereas the reported compounds showed no general cytotoxicity in other cancer cell lines tested.

  DOI：

  10.1021/jm301588r
• 作为产物：
  描述：

  3-溴-5-羟基苯甲醛 在 palladium diacetate 、 sodium carbonate 、 potassium carbonate 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 2.5h， 生成 3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyethoxy)benzaldehyde
  参考文献：
  名称：

  Optimization of 3,5-Dimethylisoxazole Derivatives as Potent Bromodomain Ligands

  摘要：

  The bromodomain protein module, which binds to acetylated lysine, is emerging as an important epigenetic therapeutic target. We report the structure-guided optimization of 3,5-dimethylisoxazole derivatives to develop potent inhibitors of the BET (bromodomain and extra terminal domain) bromodomain family with good ligand efficiency. X-ray crystal structures of the most potent compounds reveal key interactions required for high affinity at BRD4(1). Cellular studies demonstrate that the phenol and acetate derivatives of the lead compounds showed strong antiproliferative effects on MV4;11 acute myeloid leukemia cells, as shown for other BET bromodomain inhibitors and genetic BRD4 knockdown, whereas the reported compounds showed no general cytotoxicity in other cancer cell lines tested.

  DOI：

  10.1021/jm301588r

文献信息

• Optimization of 3,5-Dimethylisoxazole Derivatives as Potent Bromodomain Ligands
  作者：David S. Hewings、Oleg Fedorov、Panagis Filippakopoulos、Sarah Martin、Sarah Picaud、Anthony Tumber、Christopher Wells、Monica M. Olcina、Katherine Freeman、Andrew Gill、Alison J. Ritchie、David W. Sheppard、Angela J. Russell、Ester M. Hammond、Stefan Knapp、Paul E. Brennan、Stuart J. Conway

  DOI：10.1021/jm301588r

  日期：2013.4.25

  The bromodomain protein module, which binds to acetylated lysine, is emerging as an important epigenetic therapeutic target. We report the structure-guided optimization of 3,5-dimethylisoxazole derivatives to develop potent inhibitors of the BET (bromodomain and extra terminal domain) bromodomain family with good ligand efficiency. X-ray crystal structures of the most potent compounds reveal key interactions required for high affinity at BRD4(1). Cellular studies demonstrate that the phenol and acetate derivatives of the lead compounds showed strong antiproliferative effects on MV4;11 acute myeloid leukemia cells, as shown for other BET bromodomain inhibitors and genetic BRD4 knockdown, whereas the reported compounds showed no general cytotoxicity in other cancer cell lines tested.