N-(2,3-二氢-1,4-苯并二恶英-6-基)-1,4-二氢茚并[1,2-c]吡唑-3-胺 | 1421448-26-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 中文名称: N-(2,3-二氢-1,4-苯并二恶英-6-基)-1,4-二氢茚并[1,2-c]吡唑-3-胺
• 英文名称: N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,4-dihydroindeno[1,2-c]pyrazol-3-amine
• 英文别名: N-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,4-dihydroindeno[1,2-c]pyrazol-3-amine
• CAS: 1421448-26-1
• 化学式: C₁₈H₁₅N₃O₂
• 分子量: 305.336
• InChiKey: CGZKSZVSWAAUHE-UHFFFAOYSA-N

物化性质

• 熔点：
  144 - 148oC
• 沸点：
  543.7±50.0 °C(Predicted)
• 密度：
  1.421±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.2
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

生物活性

GN44028 是一种有效的缺氧诱导因子(HIF)-1抑制剂，其IC50值为14 nM。GN44028 能有效抑制低氧条件下HIF-1α 的转录活性，但并不影响HIF-1α mRNA的表达、HIF-1α蛋白的累积或HIF-1α/HIF-1β的异二聚化。

靶点

IC50: 14 nM (HIF-1)

反应信息

• 作为产物：
  描述：

  6-氨基-1,4-苯并二氧杂环 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 42.0h， 生成 N-(2,3-二氢-1,4-苯并二恶英-6-基)-1,4-二氢茚并[1,2-c]吡唑-3-胺
  参考文献：
  名称：

  Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors

  摘要：

  The indenopyrazole framework was investigated as a new class of HIP-la inhibitors. Indenopyrazole 21 was found to most strongly inhibit the hypoxia-induced HIF-1 alpha transcriptional activity (IC50 = 0.014 mu M) among all of the known compounds having relatively simple structures, unlike manassantins. Indenopyrazole 21 suppressed HIP-la transcriptional activity without affecting both HIF-1 alpha protein accumulation and HIF-1 alpha HIF-1 beta heterodimerization in nuclei under the hypoxic conditions, suggesting that 21 probably affected the transcriptional pathway induced by the HIF-1 alpha/HIF-1 beta heterodimer.

  DOI：

  10.1021/ml3004632

文献信息

• Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors
  作者：Hidemitsu Minegishi、Shinji Fukashiro、Hyun Seung Ban、Hiroyuki Nakamura

  DOI：10.1021/ml3004632

  日期：2013.2.14

  The indenopyrazole framework was investigated as a new class of HIP-la inhibitors. Indenopyrazole 21 was found to most strongly inhibit the hypoxia-induced HIF-1 alpha transcriptional activity (IC50 = 0.014 mu M) among all of the known compounds having relatively simple structures, unlike manassantins. Indenopyrazole 21 suppressed HIP-la transcriptional activity without affecting both HIF-1 alpha protein accumulation and HIF-1 alpha HIF-1 beta heterodimerization in nuclei under the hypoxic conditions, suggesting that 21 probably affected the transcriptional pathway induced by the HIF-1 alpha/HIF-1 beta heterodimer.