5-(4-甲基-哌嗪-1-基)-茚满-1-酮 | 866849-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 5-(4-甲基-哌嗪-1-基)-茚满-1-酮
• 英文名称: 5-(4-methylpiperazin-1-yl)indan-1-one
• 英文别名: 5-(4-Methyl-piperazin-1-YL)-indan-1-one；5-(4-methylpiperazin-1-yl)-2,3-dihydroinden-1-one
• CAS: 866849-23-2
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: MDJSXMRCQTVKRY-UHFFFAOYSA-N

物化性质

• 沸点：
  405.5±45.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-甲基-哌嗪-1-基)-茚满-1-酮 在 sodium hydride 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 苯 为溶剂， 生成 6-(4-Methylpiperazin-1-yl)-3-(5-(3-phenoxyprop-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：

  N-甲基哌嗪 、 5-氟-1-茚酮 反应 20.0h， 以60%的产率得到5-(4-甲基-哌嗪-1-基)-茚满-1-酮
  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

文献信息

• 1,4-Dihydroindeno[1,2-<i>c</i>]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel
  作者：Jürgen Dinges、Daniel H. Albert、Lee D. Arnold、Kimba L. Ashworth、Irini Akritopoulou-Zanze、Peter F. Bousquet、Jennifer J. Bouska、George A. Cunha、Steven K. Davidsen、Gilbert J. Diaz、Stevan W. Djuric、Alan F. Gasiecki、Gary A. Gintant、Vijaya J. Gracias、Christopher M. Harris、Kathryn A. Houseman、Charles W. Hutchins、Eric F. Johnson、Hu Li、Patrick A. Marcotte、Ruth L. Martin、Michael R. Michaelides、Michelle Nyein、Thomas J. Sowin、Zhi Su、Paul H. Tapang、Zhiren Xia、Henry Q. Zhang

  DOI：10.1021/jm061223o

  日期：2007.5.1

  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.