1-(4-溴苯基)-2-(2-氟苯基)乙酮 | 898784-65-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 1-(4-溴苯基)-2-(2-氟苯基)乙酮
• 英文名称: 1-(4-bromophenyl)-2-(2-fluorophenyl)ethan-1-one
• 英文别名: 4'-Bromo-2-(2-fluorophenyl)acetophenone；1-(4-bromophenyl)-2-(2-fluorophenyl)ethanone
• CAS: 898784-65-1
• 化学式: C₁₄H₁₀BrFO
• mdl: MFCD02260758
• 分子量: 293.135
• InChiKey: MDIICZPWRDMJQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-溴苯基)-2-(2-氟苯基)乙酮 在 palladium diacetate 、 sodium hydride 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 甲苯 、 mineral oil 为溶剂， 反应 0.5h， 生成 2-(2-fluorophenyl)-1-(4-(piperidin-1-yl)phenyl)propan-1-one
  参考文献：
  名称：

  Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy

  摘要：

  Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1 alpha, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1 alpha inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1 alpha inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-la inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1 alpha inhibitors that can be used in lieu of a chromene ring.

  DOI：

  10.1021/acs.jmedchem.8b00971
• 作为产物：
  描述：

  2-氟苯乙醛 在 正丁基锂 、 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 1-(4-溴苯基)-2-(2-氟苯基)乙酮
  参考文献：
  名称：

  Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy

  摘要：

  Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1 alpha, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1 alpha inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1 alpha inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-la inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1 alpha inhibitors that can be used in lieu of a chromene ring.

  DOI：

  10.1021/acs.jmedchem.8b00971

文献信息

• Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy
  作者：Hongchan An、Seungbeom Lee、Jung Min Lee、Dong Hyun Jo、Joohwan Kim、Yoo-Seong Jeong、Mi Jeong Heo、Chang Sik Cho、Hoon Choi、Ji Hae Seo、Seyeon Hwang、Jihye Lim、Taewoo Kim、Hyoung Oh Jun、Jaehoon Sim、Changjin Lim、Joonseong Hur、Jungmin Ahn、Hyun Su Kim、Seung-Yong Seo、Younghwa Na、Seok-Ho Kim、Jeewoo Lee、Jeeyeon Lee、Suk-Jae Chung、Young-Myeong Kim、Kyu-Won Kim、Sang Geon Kim、Jeong Hun Kim、Young-Ger Suh

  DOI：10.1021/acs.jmedchem.8b00971

  日期：2018.10.25

  Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1 alpha, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1 alpha inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1 alpha inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-la inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1 alpha inhibitors that can be used in lieu of a chromene ring.