3-[2-(4-adamantan-1-ylphenoxy)acetylamino]-4-hydroxy-N-(3-morpholin-4-ylpropyl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[2-(4-adamantan-1-ylphenoxy)acetylamino]-4-hydroxy-N-(3-morpholin-4-ylpropyl)benzamide
• 英文别名: 3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-4-hydroxy-N-(3-morpholine-4-yl-propyl)-benzamide；3-[[2-[4-(1-adamantyl)phenoxy]acetyl]amino]-4-hydroxy-N-(3-morpholin-4-ylpropyl)benzamide
• 化学式: C₃₂H₄₁N₃O₅
• 分子量: 547.695
• InChiKey: VKBOAIIKKGWBFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-羟基-3-硝基苯甲酸 在 palladium on activated charcoal 四丁基氟化铵 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 20.0~50.0 ℃ 、6.9 kPa 条件下， 反应 3.0h， 生成 3-[2-(4-adamantan-1-ylphenoxy)acetylamino]-4-hydroxy-N-(3-morpholin-4-ylpropyl)benzamide
  参考文献：
  名称：

  (Aryloxyacetylamino)benzoic Acid Analogues:  A New Class of Hypoxia-Inducible Factor-1 Inhibitors

  摘要：

  Structural modification of a compound discovered during screening using an HRE-dependent reporter assay has revealed a novel class of HIF-1 inhibitors, which potently inhibit the HIF-1 alpha protein accumulation and its target gene expression under hypoxic conditions in human hepatocellular carcinoma Hep3B cells.

  DOI：

  10.1021/jm0610292

文献信息

• COMPOUNDS THAT INHIBIT HIF-1 ACTIVITY, THE METHOD FOR PREPARATION THEREOF AND THE PHARMACEUTICAL COMPOSITION CONTAINING THEM AS AN EFFECTIVE COMPONENT
  申请人：Lee Jung Joon

  公开号：US20090306078A1

  公开（公告）日：2009-12-10

  Disclosed herein are an HIF-1 inhibitor, a method for the preparation thereof, and a pharmaceutical composition comprising the same as an active ingredient. The HIF-1 inhibitor shows anticancer activity thanks to the inhibition activity against HIF-1, a transcription factor which plays an important role in the growth and metastasis of cancer, but not to general cytotoxicity. Thus, the HIF-inhibitor and a pharmaceutically acceptable salt thereof can be used as a therapeutic for various cancers such as liver cancer; stomach cancer and breast cancer. Also, the compound having inhibition activity against HIF-1 is useful in the treatment of diabetic retinopathy and arthritis, which are aggravated by HIF-1-mediated VEGF expression.

  本文披露了一种HIF-1抑制剂，其制备方法，以及包含其作为活性成分的药物组合物。该HIF-1抑制剂显示抗癌活性，这归功于其对HIF-1的抑制活性，HIF-1是一种在癌症生长和转移中起重要作用的转录因子，但不具有一般细胞毒性。因此，HIF抑制剂及其药用可接受的盐可用作治疗各种癌症，如肝癌、胃癌和乳腺癌的治疗药物。此外，具有对HIF-1抑制活性的化合物在治疗由HIF-1介导的VEGF表达加重的糖尿病视网膜病变和关节炎方面是有用的。
• WO2008/4798
  申请人：——

  公开号：——

  公开（公告）日：——
• US8394799B2
  申请人：——

  公开号：US8394799B2

  公开（公告）日：2013-03-12
• (Aryloxyacetylamino)benzoic Acid Analogues:  A New Class of Hypoxia-Inducible Factor-1 Inhibitors
  作者：Kyeong Lee、Jeong Hyung Lee、Shanthaveerappa K. Boovanahalli、Yinglan Jin、Mijeoung Lee、Xuejun Jin、Jin Hwan Kim、Young-Soo Hong、Jung Joon Lee

  DOI：10.1021/jm0610292

  日期：2007.4.1

  Structural modification of a compound discovered during screening using an HRE-dependent reporter assay has revealed a novel class of HIF-1 inhibitors, which potently inhibit the HIF-1 alpha protein accumulation and its target gene expression under hypoxic conditions in human hepatocellular carcinoma Hep3B cells.