(2-{4-[5-(3,8-dihydroindeno[1,2-d] [1,2,3]triazol-6-yl)-4-(pyridin-4-yl)-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethylamine | 1251931-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (2-{4-[5-(3,8-dihydroindeno[1,2-d] [1,2,3]triazol-6-yl)-4-(pyridin-4-yl)-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethylamine
• 英文别名: 2-[4-[4-(2,4-dihydroindeno[1,2-d]triazol-6-yl)-5-pyridin-4-yl-1H-imidazol-2-yl]phenoxy]-N,N-dimethylethanamine
• CAS: 1251931-66-4
• 化学式: C₂₇H₂₅N₇O
• 分子量: 463.542
• InChiKey: SXHGHJDUEYJWBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  95.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-(2-(4-(2-(二甲基氨基)乙氧基)苯基)-5-(吡啶-4-基)-1H-咪唑-4-基)-2,3-二氢-1H-茚-1-酮 在 盐酸 、 亚硝酸特丁酯 、 一水合肼 、 potassium hydroxide 作用下， 以 甲乙醚 、 水 、 乙二醇 为溶剂， 反应 2.0h， 以1.9 mg的产率得到(2-{4-[5-(3,8-dihydroindeno[1,2-d] [1,2,3]triazol-6-yl)-4-(pyridin-4-yl)-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethylamine
  参考文献：
  名称：

  Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds

  摘要：

  V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-{5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin- 4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor. Based on this starting point, we synthesized a series of analogues leading to the discovery of 6-{2-[4-(4-methylpiperazin- 1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno[1,2-c]pyrazole (1j), with nanomolar activity in three assays: inhibition of purified mutant BRAF activity in vitro; inhibition of oncogenic BRAF-driven extracellular regulated kinase (ERK) activation in BRAF mutant melanoma cell lines; and inhibition of proliferation in these cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.031