4-[4-(2,4-dihydroindeno[1,2-c]pyrazol-6-yl)-5-(pyridin-4-yl)-furan-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester | 1251931-48-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: 4-[4-(2,4-dihydroindeno[1,2-c]pyrazol-6-yl)-5-(pyridin-4-yl)-furan-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester
• CAS: 1251931-48-2
• 化学式: C₂₉H₂₉N₅O₄
• 分子量: 511.58
• InChiKey: MJZDKDBJCRTJLE-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  4-[4-(2,4-dihydroindeno[1,2-c]pyrazol-6-yl)-5-(pyridin-4-yl)-furan-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 、 水 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.0h， 以100%的产率得到[4-(2,4-dihydroindeno[1,2-c]pyrazol-6-yl)-5-(pyridin-4-yl)-furan-2-yl]-piperazin-1-yl-methanone
  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：

  C₃₁H₃₄N₄O₅ 在 一水合肼 、 溶剂黄146 作用下， 以70 mg的产率得到4-[4-(2,4-dihydroindeno[1,2-c]pyrazol-6-yl)-5-(pyridin-4-yl)-furan-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester
  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