N,N-diisopropyl-6-(7-hydroxy-6,7-dihydro-6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthamide | 1346155-86-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N,N-diisopropyl-6-(7-hydroxy-6,7-dihydro-6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthamide
• CAS: 1346155-86-9
• 化学式: C₂₅H₃₁N₃O₂
• 分子量: 405.54
• InChiKey: TXAVVJXARQISNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.57
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  58.36
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N,N-diisopropyl-6-(7-hydroxy-6,7-dihydro-6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthamide 、 甲胺 在 正丁基锂 、 水 、 sodium chloride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 16.33h， 以33%的产率得到6-(7-hydroxy-6,7-dihydro-6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-yl)-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
• 作为产物：
  描述：

  6-溴-2-萘甲酸 在 正丁基锂 、 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 5.5h， 生成 N,N-diisopropyl-6-(7-hydroxy-6,7-dihydro-6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-yl)-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