| 1346155-43-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• CAS: 1346155-43-8
• 化学式: C₁₉H₂₁N₃O₂
• 分子量: 323.395
• InChiKey: XEYZCKZMDNQROP-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  78.01
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide 在 Chiralpak AD column 作用下， 以 乙醇 、 正己烷 为溶剂， 以48%的产率得到(S)-(-)-6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide
  参考文献：
  名称：

  1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4

  摘要：

  A series of 1,1-diarylalkene derivatives were prepared to optimize the properties of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC(50) = 54 nM) and antitubulin activity (HCT-116 IC(50) = 34 nM and tubulin polymerization IC(50) similar to 1 mu M). While the nitrile group at the alkene terminus was generally required for potent antiproliferative activity, its replacement was tolerated if there was a hydroxyl or amino group on one of the aryl rings. Conveniently, this group could also serve as a handle for amino acid derivatization to improve the compounds' solubility. The glycinamide analog 45 showed significant efficacy in the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at 20 mg/kg qd. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.068