2-(3,4-dimethoxyphenyl)-1-(4-hydroxy-2-methoxyphenyl)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-(3,4-dimethoxyphenyl)-1-(4-hydroxy-2-methoxyphenyl)propan-1-one
• 英文别名: 2-(3,4-Dimethoxyphenyl)-1-(4-hydroxy-2-methoxyphenyl)propan-1-one
• 化学式: C₁₈H₂₀O₅
• 分子量: 316.354
• InChiKey: OCLYKFCEQYXXIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-1-(4-hydroxy-2-methoxyphenyl)propan-1-one 在 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.0h， 生成 2-(3,4-dimethoxyphenyl)-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
• 作为产物：
  描述：

  4-溴-3-甲氧基苯酚 在 盐酸 、 正丁基锂 、 sodium hydride 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 7.0h， 生成 2-(3,4-dimethoxyphenyl)-1-(4-hydroxy-2-methoxyphenyl)propan-1-one
  参考文献：
  名称：

  생체 시계 조절용 화합물 및 이의 용도

  摘要：

  本发明涉及一种依赖于构成生物钟的核心基因Rev-erbα的新化合物的活性，并且可以制造包含本发明新化合物作为有效成分的生物节律调节药物组合物，使用抑制Pai-1或Citrate synthase活性的药物组合物来调节生物周期节律，治疗代谢性疾病，包括动脉硬化，免疫性疾病和心血管疾病。

  公开号：

  KR20170033104A

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。