1–(4-(2-fluorophenyl)piperazin-1-yl)-4-methylphthalazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1–(4-(2-fluorophenyl)piperazin-1-yl)-4-methylphthalazine
• 英文别名: 1-[4-(2-Fluorophenyl)piperazin-1-yl]-4-methylphthalazine
• 化学式: C₁₉H₁₉FN₄
• 分子量: 322.385
• InChiKey: ALZIBSVSTZGIRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-甲基酞嗪-1(2H)-酮 在 potassium carbonate 、 potassium iodide 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 1–(4-(2-fluorophenyl)piperazin-1-yl)-4-methylphthalazine
  参考文献：
  名称：

  Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition

  摘要：

  In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds (6b, 6e, 7b, 13a, 13c, 16a, 16d and 17a) exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI(50) values ranging from 0.15 to 8.41 mu M. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas (12b, 12c and 13c) with IC(50)s of 4.4, 2.7 and 2.5 mu M, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 mu M, respectively. Additionally, compounds (7b, 13c and 16a) were found to induce cell cycle arrest at S phase boundary. Compound 7b triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death.

  DOI：

  10.1080/14756366.2019.1642883

文献信息

• Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition
  作者：Salwa Elmeligie、Asmaa M. Aboul-Magd、Deena S. Lasheen、Tamer M. Ibrahim、Tamer M. Abdelghany、Sohair M. Khojah、Khaled A. M. Abouzid

  DOI：10.1080/14756366.2019.1642883

  日期：2019.1.1

  In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds (6b, 6e, 7b, 13a, 13c, 16a, 16d and 17a) exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI(50) values ranging from 0.15 to 8.41 mu M. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas (12b, 12c and 13c) with IC(50)s of 4.4, 2.7 and 2.5 mu M, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 mu M, respectively. Additionally, compounds (7b, 13c and 16a) were found to induce cell cycle arrest at S phase boundary. Compound 7b triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death.