7-((1H-1,2,4-triazol-1-yl)methyl)-3-(5-bromothiophen-3-yl)-1,4-dihydroindeno[1,2-c]pyrazole | 866851-31-2

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 7-((1H-1,2,4-triazol-1-yl)methyl)-3-(5-bromothiophen-3-yl)-1,4-dihydroindeno[1,2-c]pyrazole
• 英文别名: 3-(5-Bromothiophen-3-yl)-7-(1,2,4-triazol-1-ylmethyl)-1,4-dihydroindeno[1,2-c]pyrazole
• CAS: 866851-31-2
• 化学式: C₁₇H₁₂BrN₅S
• 分子量: 398.286
• InChiKey: WDVUGXPOQNRCFA-UHFFFAOYSA-N

物化性质

• 沸点：
  637.4±65.0 °C(Predicted)
• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  87.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-((1H-1,2,4-triazol-1-yl)methyl)-3-(5-bromothiophen-3-yl)-1,4-dihydroindeno[1,2-c]pyrazole 、 3-(2-methoxyethoxy)prop-1-yne 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 三乙胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以22%的产率得到7-((1H-1,2,4-triazol-1-yl)methyl)-3-(5-(3-(2-methoxyethoxy)-prop-1-ynyl)thiophen-3-yl)-1,4-dihydroindeno[1,2-c]pyrazole
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o
• 作为产物：
  描述：

  在 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 以3.0 mg的产率得到7-((1H-1,2,4-triazol-1-yl)methyl)-3-(5-bromothiophen-3-yl)-1,4-dihydroindeno[1,2-c]pyrazole
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o