1-(3-methoxyphenyl)-2-[4-(4-phenylphthalazin-1-yl)piperazin-1-yl]ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-methoxyphenyl)-2-[4-(4-phenylphthalazin-1-yl)piperazin-1-yl]ethanone
• 英文别名: 1-(3-Methoxyphenyl)-2-[4-(4-phenylphthalazin-1-yl)piperazin-1-yl]ethanone
• 化学式: C₂₇H₂₆N₄O₂
• 分子量: 438.529
• InChiKey: OJJSXTLTZWSYER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  邻苯甲酰苯甲酸 在 potassium carbonate 、 sodium hydroxide 、 硫酸肼 、 三氯氧磷 作用下， 以 异丙醇 、 丙酮 为溶剂， 反应 12.0h， 生成 1-(3-methoxyphenyl)-2-[4-(4-phenylphthalazin-1-yl)piperazin-1-yl]ethanone
  参考文献：
  名称：

  1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: Synthesis and in vitro biological evaluation

  摘要：

  In our endeavor towards the development of effective VEGFR-2 inhibitors, three novel series of phthalazine derivatives based on 1-piperazinyl-4-arylphthalazine scaffold were synthesized. All the newly prepared phthalazines 16a-k, 18a-e and 21a-g were evaluated in vitro for their inhibitory activity against VEGFR-2. In particular, compounds 16k and 21d potently inhibited VEGFR-2 at sub-micromolar IC50 values 0.35 +/- 0.03 and 0.40 +/- 0.04 mu M, respectively. Moreover, seventeen selected compounds 16c-e, 16g, 16h, 16j, 16k, 18c-e and 21a-g were evaluated for their in vitro anticancer activity according to US-NCI protocol, where compounds 16k and 21d proved to be the most potent anticancer agents. While, compound 16k exhibited potent broad spectrum anticancer activity with full panel GI(50) (MG-MID) value of 3.62 mu M, compound 21d showed high selectivity toward leukemia and prostate cancer subpanels [subpanel GI(50) (MG-MID) 3.51 and 5.15 mu M, respectively]. Molecular docking of compounds16k and 21d into VEGFR-2 active site was performed to explore their potential binding mode. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.053

文献信息

• 1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: Synthesis and in vitro biological evaluation
  作者：Sahar M. Abou-Seri、Wagdy M. Eldehna、Mamdouh M. Ali、Dalal A. Abou El Ella

  DOI：10.1016/j.ejmech.2015.10.053

  日期：2016.1

  In our endeavor towards the development of effective VEGFR-2 inhibitors, three novel series of phthalazine derivatives based on 1-piperazinyl-4-arylphthalazine scaffold were synthesized. All the newly prepared phthalazines 16a-k, 18a-e and 21a-g were evaluated in vitro for their inhibitory activity against VEGFR-2. In particular, compounds 16k and 21d potently inhibited VEGFR-2 at sub-micromolar IC50 values 0.35 +/- 0.03 and 0.40 +/- 0.04 mu M, respectively. Moreover, seventeen selected compounds 16c-e, 16g, 16h, 16j, 16k, 18c-e and 21a-g were evaluated for their in vitro anticancer activity according to US-NCI protocol, where compounds 16k and 21d proved to be the most potent anticancer agents. While, compound 16k exhibited potent broad spectrum anticancer activity with full panel GI(50) (MG-MID) value of 3.62 mu M, compound 21d showed high selectivity toward leukemia and prostate cancer subpanels [subpanel GI(50) (MG-MID) 3.51 and 5.15 mu M, respectively]. Molecular docking of compounds16k and 21d into VEGFR-2 active site was performed to explore their potential binding mode. (C) 2015 Elsevier Masson SAS. All rights reserved.