N1-(phthalazin-1-yl)benzene-1,4-diamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N1-(phthalazin-1-yl)benzene-1,4-diamine
• 英文别名: 4-N-phthalazin-1-ylbenzene-1,4-diamine
• 化学式: C₁₄H₁₂N₄
• mdl: MFCD12424573
• 分子量: 236.276
• InChiKey: OMPSCGCGBDUSEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N1-(phthalazin-1-yl)benzene-1,4-diamine 、 4-氯-3-三氟甲基异氰酸苯酯 以 N,N-二甲基甲酰胺 为溶剂， 以49%的产率得到1–(4-chloro-3-(trifluoromethyl)phenyl)-3–(4-(phthalazin-1-ylamino)phenyl)urea
  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
• 作为产物：
  描述：

  1-(2H)-酞嗪酮 在 三氯氧磷 作用下， 以 仲丁醇 为溶剂， 反应 2.0h， 生成 N1-(phthalazin-1-yl)benzene-1,4-diamine
  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

• PHARMACEUTICAL COMPOUNDS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cai Sui Xiong

  公开号：US20080020985A1

  公开（公告）日：2008-01-24

  Disclosed are 1-arylamino-phthalazines, 4-arylamino-benzo[d][1,2,3]triazines, and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明披露了1-芳基氨基-菲啶嗪、4-芳基氨基苯并[d][1,2,3]三嗪及其类似物，它们有效激活半胱氨酸蛋白酶和诱导细胞凋亡。本发明的化合物在治疗各种临床病症中具有用途，这些病症中存在不受控制的异常细胞生长和扩散。
• US7842805B2
  申请人：——

  公开号：US7842805B2

  公开（公告）日：2010-11-30
• 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.