5-{2-[4-(2-dimethylaminoethoxy)-phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl}-indan-1-one O-methyloxime | 405554-85-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-{2-[4-(2-dimethylaminoethoxy)-phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl}-indan-1-one O-methyloxime
• 英文别名: 2-[4-[4-(1-methoxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-yl-1H-imidazol-2-yl]phenoxy]-N,N-dimethylethanamine
• CAS: 405554-85-0
• 化学式: C₂₈H₂₉N₅O₂
• 分子量: 467.571
• InChiKey: KYSZSACCZCQBOT-UHFFFAOYSA-N

物化性质

• 沸点：
  661.5±65.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-{2-[4-(2-dimethylaminoethoxy)-phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl}-indan-1-one O-methyloxime 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 以23%的产率得到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
  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
• 作为产物：
  描述：

  1-(1-methoxyiminoindan-5-yl)-2-(pyridin-4-yl)-ethane-1,2-dione 、 4-[2-(二甲胺基)乙氧基]苯甲醛 在 ammonium acetate 、 溶剂黄146 作用下， 以29%的产率得到5-{2-[4-(2-dimethylaminoethoxy)-phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl}-indan-1-one O-methyloxime
  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