6-(Aziridin-1-yl)-2-phenylquinoline-5,8-dione | 618886-07-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-(Aziridin-1-yl)-2-phenylquinoline-5,8-dione
• CAS: 618886-07-0
• 化学式: C₁₇H₁₂N₂O₂
• 分子量: 276.294
• InChiKey: QVIFZZCONYCRNV-UHFFFAOYSA-N

物化性质

• 熔点：
  183 °C (decomp)
• 沸点：
  502.0±50.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  50
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(Aziridin-1-yl)-2-phenylquinoline-5,8-dione 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 0.18h， 以71%的产率得到6-(2-Chloroethylamino)-2-phenylquinoline-5,8-dione
  参考文献：
  名称：

  Design of quinolinedione-Based geldanamycin analogues

  摘要：

  Quinoline-5,8-dione-based compounds were designed from the structure of the geldanamycin-bound Hsp-90 active site. The active site model predicted that aromatic substituents should be present at the 2-position, to take advantage of a hydrophobic pocket, and amino substituents should be present at the 6- or 7-position. COMPARE analysis revealed that the LC50 profile of 2-phenyl-6-(2-chloroethylamino)quinoline-5,8-dione has the highest geldanamycin-like activity (0.74 correlation coefficient). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00650-4
• 作为产物：
  描述：

  2-phenyl-5,8-dimethoxyquinoline 在 ammonium cerium(IV) nitrate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 2.75h， 生成 6-(Aziridin-1-yl)-2-phenylquinoline-5,8-dione
  参考文献：
  名称：

  Design of quinolinedione-Based geldanamycin analogues

  摘要：

  Quinoline-5,8-dione-based compounds were designed from the structure of the geldanamycin-bound Hsp-90 active site. The active site model predicted that aromatic substituents should be present at the 2-position, to take advantage of a hydrophobic pocket, and amino substituents should be present at the 6- or 7-position. COMPARE analysis revealed that the LC50 profile of 2-phenyl-6-(2-chloroethylamino)quinoline-5,8-dione has the highest geldanamycin-like activity (0.74 correlation coefficient). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00650-4

文献信息

• Discovery of Quinolinediones Exhibiting a Heat Shock Response and Angiogenesis Inhibition
  作者：Robert H. J. Hargreaves、Cynthia L. David、Luke J. Whitesell、Daniel V. LaBarbera、Akmal Jamil、Jean C. Chapuis、Edward B. Skibo

  DOI：10.1021/jm7014099

  日期：2008.4.1

  A series of substituted quinoline-5,8-diones were synthesized and evaluated as inhibitors of the chaperone protein Hsp90 using two assays: competition for binding to C-terminal ATP-binding site and competition for binding to N-terminal ATP-binding site. In addition, the ability of the compounds to induce the heat shock response was determined using a reporter fibroblast cell line. Of all the compounds assayed, only 6-aziridinyl-2-biphenylquinoline-5,8-dione induced a heat shock response and did so without interacting at the ATP binding sites of Hsp90. COMPARE analysis was carried out on quinoline-5,8-diones active in the National Cancer Institute's 60-cell line screen with the goal of discovering quinoline-5,8-dione structures that interact with other cellular targets (molecular targets) important for cancer chemotherapy. COMPARE analysis led to the discovery of a combretastatin- like quinoline-5,8-dione structure that, in fact, inhibited angiogenesis.
• Design of quinolinedione-Based geldanamycin analogues
  作者：Robert Hargreaves、Cynthia L. David、Luke Whitesell、Edward B. Skibo

  DOI：10.1016/s0960-894x(03)00650-4

  日期：2003.9

  Quinoline-5,8-dione-based compounds were designed from the structure of the geldanamycin-bound Hsp-90 active site. The active site model predicted that aromatic substituents should be present at the 2-position, to take advantage of a hydrophobic pocket, and amino substituents should be present at the 6- or 7-position. COMPARE analysis revealed that the LC50 profile of 2-phenyl-6-(2-chloroethylamino)quinoline-5,8-dione has the highest geldanamycin-like activity (0.74 correlation coefficient). (C) 2003 Elsevier Ltd. All rights reserved.