2-(2-fluorophenyl)-1-(2-methoxy-4-(piperidin-1-yl)phenyl)propan-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - α-甲基脱氧安息香黄酮
• 英文名称: 2-(2-fluorophenyl)-1-(2-methoxy-4-(piperidin-1-yl)phenyl)propan-1-one
• 英文别名: 2-(2-Fluorophenyl)-1-(2-methoxy-4-piperidin-1-ylphenyl)propan-1-one；2-(2-fluorophenyl)-1-(2-methoxy-4-piperidin-1-ylphenyl)propan-1-one
• 化学式: C₂₁H₂₄FNO₂
• 分子量: 341.425
• InChiKey: AMRMHIWSDXURTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴-3-甲氧基苯酚 在 盐酸 、 正丁基锂 、 palladium diacetate 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 、 caesium carbonate 、 戴斯-马丁氧化剂 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 13.5h， 生成 2-(2-fluorophenyl)-1-(2-methoxy-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

文献信息

• NOVEL HIF-1ALPHA INHIBITOR, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING ANGIOGENESIS-ASSOCIATED EYE DISEASE, CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION

  公开号：US20210188753A1

  公开（公告）日：2021-06-24

  Disclosed are a novel hypoxia-inducible factor 1a (HIF-1α) inhibitor, a method of preparing the same, and a pharmaceutical composition for preventing or treating an angiogenesis-related eye disease containing the same as an active ingredient. The compound of Example provided according to an embodiment of the present invention is capable of effectively inhibiting HIF-1α and is thus useful as a pharmaceutical composition for preventing or treating an angiogenesis-related eye disease.

  揭示了一种新型缺氧诱导因子1α（HIF-1α）抑制剂，一种制备该抑制剂的方法，以及一种预防或治疗与血管生成相关的眼部疾病的药物组合物，该组合物含有该抑制剂作为活性成分。根据本发明实施例提供的示例化合物能够有效抑制HIF-1α，因此可用作预防或治疗与血管生成相关的眼部疾病的药物组合物。
• NOVEL HIF-1alfa INHIBITOR, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING ANGIOGENESIS-ASSOCIATED EYE DISEASE, CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Seoul National University R & DB Foundation

  公开号：EP3845516A1

  公开（公告）日：2021-07-07

  Disclosed are a novel hypoxia-inducible factor 1α (HIF-1α) inhibitor, a method of preparing the same, and a pharmaceutical composition for preventing or treating an angiogenesis-related eye disease containing the same as an active ingredient. The compound of Example provided according to an embodiment of the present invention is capable of effectively inhibiting HIF-1α and is thus useful as a pharmaceutical composition for preventing or treating an angiogenesis-related eye disease.

  本发明公开了一种新型低氧诱导因子 1α（HIF-1α）抑制剂、一种制备方法和一种预防或治疗血管生成相关眼病的药物组合物，其中含有该抑制剂作为活性成分。根据本发明一个实施例提供的实施例化合物能够有效抑制HIF-1α，因此可用作预防或治疗血管生成相关眼病的药物组合物。