(E)-3-(2-bromophenyl)-1-(3-bromophenyl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(2-bromophenyl)-1-(3-bromophenyl)prop-2-en-1-one
• 化学式: C₁₅H₁₀Br₂O
• 分子量: 366.052
• InChiKey: CPLQSQQPWAOKOC-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (E)-3-(2-bromophenyl)-1-(3-bromophenyl)prop-2-en-1-one 在 sodium tetrahydroborate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (±)-(cis)-7-(2-bromophenyl)-5-(3-bromophenyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Isoform-Selective and Stereoselective Inhibition of Hypoxia Inducible Factor-2

  摘要：

  Hypoxia inducible factor (HIF) transcription factors reside at the center of signaling pathways used by mammalian cells to sense and respond to low oxygen levels. While essential to maintain oxygen homeostasis, misregulation of HIF protein activity correlates with tumor development and metastasis. To provide artificial routes to target misregulated HIF activity, we identified small molecule antagonists of the HIF-2 transcription factor that bind an internal cavity within the C-terminal PAS domain of the HIF-2 alpha subunit. Here we describe a new class of chiral small molecule ligands that provide the highest affinity binding, the most effective, isoform-selective inhibition of HIP-2 in cells, and trigger the largest protein conformation changes reported to date. The current results further illuminate the molecular mechanism of HIF-2 antagonism and suggest additional routes to develop higher affinity and potency HIF-2 antagonists.

  DOI：

  10.1021/acs.jmedchem.5b00529
• 作为产物：
  描述：

  3'-溴苯乙酮 、 邻溴苯甲醛 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以26%的产率得到(E)-3-(2-bromophenyl)-1-(3-bromophenyl)prop-2-en-1-one
  参考文献：
  名称：

  Isoform-Selective and Stereoselective Inhibition of Hypoxia Inducible Factor-2

  摘要：

  Hypoxia inducible factor (HIF) transcription factors reside at the center of signaling pathways used by mammalian cells to sense and respond to low oxygen levels. While essential to maintain oxygen homeostasis, misregulation of HIF protein activity correlates with tumor development and metastasis. To provide artificial routes to target misregulated HIF activity, we identified small molecule antagonists of the HIF-2 transcription factor that bind an internal cavity within the C-terminal PAS domain of the HIF-2 alpha subunit. Here we describe a new class of chiral small molecule ligands that provide the highest affinity binding, the most effective, isoform-selective inhibition of HIP-2 in cells, and trigger the largest protein conformation changes reported to date. The current results further illuminate the molecular mechanism of HIF-2 antagonism and suggest additional routes to develop higher affinity and potency HIF-2 antagonists.

  DOI：

  10.1021/acs.jmedchem.5b00529

文献信息

• Isoform-Selective and Stereoselective Inhibition of Hypoxia Inducible Factor-2
  作者：Thomas H. Scheuermann、Daniel Stroud、Christopher E. Sleet、Liela Bayeh、Cameron Shokri、Hanzhi Wang、Charles G. Caldwell、Jamie Longgood、John B. MacMillan、Richard K. Bruick、Kevin H. Gardner、Uttam K. Tambar

  DOI：10.1021/acs.jmedchem.5b00529

  日期：2015.8.13

  Hypoxia inducible factor (HIF) transcription factors reside at the center of signaling pathways used by mammalian cells to sense and respond to low oxygen levels. While essential to maintain oxygen homeostasis, misregulation of HIF protein activity correlates with tumor development and metastasis. To provide artificial routes to target misregulated HIF activity, we identified small molecule antagonists of the HIF-2 transcription factor that bind an internal cavity within the C-terminal PAS domain of the HIF-2 alpha subunit. Here we describe a new class of chiral small molecule ligands that provide the highest affinity binding, the most effective, isoform-selective inhibition of HIP-2 in cells, and trigger the largest protein conformation changes reported to date. The current results further illuminate the molecular mechanism of HIF-2 antagonism and suggest additional routes to develop higher affinity and potency HIF-2 antagonists.