methyl 4-(1-(methoxyimino)-2,3-dihydro-1H-inden-5-yl)-5-(pyridin-4-yl)furan-2-carboxylate | 1251931-25-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: methyl 4-(1-(methoxyimino)-2,3-dihydro-1H-inden-5-yl)-5-(pyridin-4-yl)furan-2-carboxylate
• CAS: 1251931-25-5
• 化学式: C₂₁H₁₈N₂O₄
• 分子量: 362.385
• InChiKey: HBIUMHMYDFLBAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  73.92
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 4-(1-(methoxyimino)-2,3-dihydro-1H-inden-5-yl)-5-(pyridin-4-yl)furan-2-carboxylate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.5h， 以68%的产率得到2-(4-pyridyl)-3-(5-indanyl-N-O-methyloxime)-furanyl-5-carboxylic acid
  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-(methoxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid 、 methyl 2-(4-pyridyl)-3-bromofuranylcarboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 三苯胂 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以69%的产率得到methyl 4-(1-(methoxyimino)-2,3-dihydro-1H-inden-5-yl)-5-(pyridin-4-yl)furan-2-carboxylate
  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