tert-butyl (S)-3-(6-(diisopropylcarbamoyl)naphthalen-2-yl)-3-hydroxy-3-(1-trityl-1H-imidazol-4-yl)propanoate | 426219-58-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: tert-butyl (S)-3-(6-(diisopropylcarbamoyl)naphthalen-2-yl)-3-hydroxy-3-(1-trityl-1H-imidazol-4-yl)propanoate
• 英文别名: tert-butyl (3S)-3-[6-[di(propan-2-yl)carbamoyl]naphthalen-2-yl]-3-hydroxy-3-(1-tritylimidazol-4-yl)propanoate
• CAS: 426219-58-1
• 化学式: C₄₆H₄₉N₃O₄
• 分子量: 707.913
• InChiKey: FINKYFPPWBUNLE-GWHBCOKCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  84.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-bromo-N,N-diisopropyl-2-naphthamide 在 manganese(IV) oxide 、 正丁基锂 、 三甲基氯硅烷 、 锌 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 8.17h， 生成 tert-butyl (S)-3-(6-(diisopropylcarbamoyl)naphthalen-2-yl)-3-hydroxy-3-(1-trityl-1H-imidazol-4-yl)propanoate
  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