6-[(1S)-1-(1-[(4-bromophenyl)sulfonyl]-1H-imidazol-4-yl)-1-hydroxy-2-methylpropyl]-N-methylnaphthalene-2-carboxamide | 1346155-40-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-[(1S)-1-(1-[(4-bromophenyl)sulfonyl]-1H-imidazol-4-yl)-1-hydroxy-2-methylpropyl]-N-methylnaphthalene-2-carboxamide
• CAS: 1346155-40-5
• 化学式: C₂₅H₂₄BrN₃O₄S
• 分子量: 542.453
• InChiKey: QSPJILNATRXJTM-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  101.29
• 氢给体数：
  2.0
• 氢受体数：
  6.0

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 三乙胺 作用下， 以 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 6-[(1S)-1-(1-[(4-bromophenyl)sulfonyl]-1H-imidazol-4-yl)-1-hydroxy-2-methylpropyl]-N-methylnaphthalene-2-carboxamide
  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