4-phenyl-1-(piperazin-1-yl)phthalazine | 30437-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-phenyl-1-(piperazin-1-yl)phthalazine
• 英文别名: 1-phenyl-4-piperazin-1-yl-phthalazine；1-Phenyl-4-(piperazin-1-yl)phthalazine；1-phenyl-4-piperazin-1-ylphthalazine
• CAS: 30437-09-3
• 化学式: C₁₈H₁₈N₄
• 分子量: 290.368
• InChiKey: GCMUHGJHZLTCPV-UHFFFAOYSA-N

物化性质

• 沸点：
  548.0±45.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-溴苯乙酮 、 4-phenyl-1-(piperazin-1-yl)phthalazine 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以77%的产率得到1-phenyl-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
• 作为产物：
  描述：

  邻苯甲酰苯甲酸 在 sodium hydroxide 、 硫酸肼 、 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 9.0h， 生成 4-phenyl-1-(piperazin-1-yl)phthalazine
  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

• DISUBSTITUTED PHTHALAZINE HEDGEHOG PATHWAY ANTAGONISTS
  申请人：Bastian Jolie Anne

  公开号：US20110190304A1

  公开（公告）日：2011-08-04

  The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.

  本发明提供了一种新型的1,4-二取代邻苯二酮刺猬途径拮抗剂，可用于治疗癌症。
• Design of 1-piperazinyl-4-arylphthalazines as potent Smoothened antagonists
  作者：Brian S. Lucas、Wade Aaron、Songzhu An、Richard J. Austin、Matthew Brown、Hon Chan、Angela Chong、Randall Hungate、Tom Huang、Ben Jiang、Michael G. Johnson、Jacob A. Kaizerman、Gary Lee、Dustin L. McMinn、Jessica Orf、Jay P. Powers、Minqing Rong、Maria M. Toteva、Craig Uyeda、Dineli Wickramasinghe、Guifen Xu、Qiuping Ye、Wendy Zhong

  DOI：10.1016/j.bmcl.2010.04.110

  日期：2010.6

  The Hedgehog (Hh) signaling pathway regulates cell proliferation and differentiation in developing tissues, and abnormal activation of the Hh pathway has been linked to several tumor subsets. As a transducer of Hh signaling, the GPCR-like protein Smoothened (Smo) is a promising target for disruption of unregulated Hh signaling. A series of 1-amino-4-arylphthalazines was developed as potent and orally bioavailable inhibitors of Smo. A representative compound from this class demonstrated significant tumor volume reduction in a mouse medulloblastoma model. (C) 2010 Elsevier Ltd. All rights reserved.
• US8404687B2
  申请人：——

  公开号：US8404687B2

  公开（公告）日：2013-03-26
• [EN] DISUBSTITUTED PHTHALAZINE HEDGEHOG PATHWAY ANTAGONISTS<br/>[FR] ANTAGONISTES PHTALAZINE DISUBSTITUÉE DE LA VOIE DE SIGNALISATION HEDGEHOG
  申请人：LILLY CO ELI

  公开号：WO2010062507A1

  公开（公告）日：2010-06-03

  The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.
• 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.