1-(piperazin-1-yl)-4-(pyridin-4-ylmethyl)-phthalazine | 1236306-14-1

• 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-(piperazin-1-yl)-4-(pyridin-4-ylmethyl)-phthalazine
• 英文别名: 1-Piperazin-1-yl-4-(pyridin-4-ylmethyl)phthalazine
• CAS: 1236306-14-1
• 化学式: C₁₈H₁₉N₅
• 分子量: 305.382
• InChiKey: BTWLXCDDRYUUMJ-UHFFFAOYSA-N

物化性质

• 熔点：
  209-210 °C
• 沸点：
  595.1±45.0 °C(predicted)
• 密度：
  1.217±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  53.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(piperazin-1-yl)-4-(pyridin-4-ylmethyl)-phthalazine 、 2-氯-N-(3,4-二氟苯基)乙酰胺 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以36%的产率得到N-(3,4-difluorophenyl)-2-(4-(4-(pyridin-4-ylmethyl)phthalazin-1-yl)piperazin-1-yl)acetamide
  参考文献：
  名称：

  Synthesis and antitumor activities of novel 1,4-disubstituted phthalazine derivatives

  摘要：

  In an attempt to develop potent and selective antitumor agents, a series of novel 1,4-disubstituted phthalazine derivatives was designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. Among them, seven compounds (7a-7e, 7j and 7i) displayed excellent selectivity for MDA-MB-231 cells with IC(50) values in the nM range, a desirable range for pharmacological testing. The most promising compound, 7a (IC(50) = 3.79 mu M, 2.32 mu M, 0.84 nM), was 5.6-, 10.8- and 6.9 x 10(4)- times more active than PTK-787 (IC(50) = 21.16 mu M, 22.11 mu M, 57.72 mu M), respectively. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.016
• 作为产物：
  描述：

  苯酞 在 sodium methylate 、 一水合肼 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 丙酸乙酯 、 乙腈 为溶剂， 反应 14.0h， 生成 1-(piperazin-1-yl)-4-(pyridin-4-ylmethyl)-phthalazine
  参考文献：
  名称：

  新型1,4-取代酞嗪衍生物的合成及抗肿瘤活性

  摘要：

  设计并合成了一系列的1,4-取代的酞嗪衍生物。筛选所有制备的化合物在体外对A549，HT-29和MDA-MB-231细胞系的细胞毒活性。其中，化合物7a – 7h对MDA-MB-231细胞系具有优异的选择性，IC 50值为1 nmol / L至0.92μmol/ L。对这些衍生物进行了初步的SAR研究。

  DOI：

  10.1016/j.cclet.2010.04.004

文献信息

• Synthesis and antitumor activities of novel 1,4-substituted phthalazine derivatives
  作者：Shu Lan Zhang、Ya Jing Liu、Yan Fang Zhao、Qiu Ting Guo、Ping Gong

  DOI：10.1016/j.cclet.2010.04.004

  日期：2010.9

  A series of 1,4-substituted phthalazine derivatives were designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. Among them, compounds 7a–7h showed excellent selectivity for MDA-MB-231 cell line with IC50 values from 1 nmol/L to 0.92 μmol/L. A preliminary SAR study of these derivatives was performed.

  设计并合成了一系列的1,4-取代的酞嗪衍生物。筛选所有制备的化合物在体外对A549，HT-29和MDA-MB-231细胞系的细胞毒活性。其中，化合物7a – 7h对MDA-MB-231细胞系具有优异的选择性，IC 50值为1 nmol / L至0.92μmol/ L。对这些衍生物进行了初步的SAR研究。
• Synthesis and Cytotoxic Evaluation of Some New Phthalazinylpiperazine Derivatives
  作者：Yajing Liu、Shulan Zhang、Ye Li、Jianqiang Wang、Yu Song、Ping Gong

  DOI：10.1002/ardp.201100250

  日期：2012.4

  A new series of 1,4‐disubstituted phthalazinylpiperazine derivatives 7a–f, 12a–f and 20a–f were designed and synthesized in order to develop potent and selective antitumor agents. The target compounds were screened for their cytotoxic activities against A549, HT‐29 and MDA‐MB‐231 cancer cell lines in vitro. Among them, compounds 7a–f exhibited excellent selectivity for MDA‐MB‐231 with IC50 values ranging

  设计并合成了一系列新的 1,4-二取代酞嗪基哌嗪衍生物 7a-f、12a-f 和 20a-f，以开发有效和选择性的抗肿瘤剂。在体外筛选了目标化合物对 A549、HT-29 和 MDA-MB-231 癌细胞系的细胞毒活性。其中，化合物 7a-f 对 MDA-MB-231 表现出优异的选择性，IC50 值范围为 0.013 µM 至 0.079 µM。最有希望的化合物 7e（IC50 = 2.19 µM、2.19 µM、0.013 µM）的活性分别是 vatalanib（IC50 = 20.27 µM、21.96 µM、63.90 µM）的 9.3、10 和 4.9 × 103 倍。
• Synthesis and antitumor activities of novel 1,4-disubstituted phthalazine derivatives
  作者：Shulan Zhang、Yanfang Zhao、Yajing Liu、Dong Chen、Weihuan Lan、Qiaoling Zhao、Chengcheng Dong、Lin Xia、Ping Gong

  DOI：10.1016/j.ejmech.2010.05.016

  日期：2010.8

  In an attempt to develop potent and selective antitumor agents, a series of novel 1,4-disubstituted phthalazine derivatives was designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. Among them, seven compounds (7a-7e, 7j and 7i) displayed excellent selectivity for MDA-MB-231 cells with IC(50) values in the nM range, a desirable range for pharmacological testing. The most promising compound, 7a (IC(50) = 3.79 mu M, 2.32 mu M, 0.84 nM), was 5.6-, 10.8- and 6.9 x 10(4)- times more active than PTK-787 (IC(50) = 21.16 mu M, 22.11 mu M, 57.72 mu M), respectively. (C) 2010 Elsevier Masson SAS. All rights reserved.