N-(4-bromophthalazin-1-yl)benzene-1,4-diamine | 1402423-58-8

• 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: N-(4-bromophthalazin-1-yl)benzene-1,4-diamine
• 英文别名: N¹-(4-bromophthalazin-1-yl)benzene-1,4-diamine；4-N-(4-bromophthalazin-1-yl)benzene-1,4-diamine
• CAS: 1402423-58-8
• 化学式: C₁₄H₁₁BrN₄
• 分子量: 315.172
• InChiKey: YXPMIMHGFZYDFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 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：

  N-(4-bromophthalazin-1-yl)benzene-1,4-diamine 在 sodium acetate 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-((4-oxo-3,4-dihydrophthalazin-1-yl) amino)phenyl)urea
  参考文献：
  名称：

  The synthesis and anti‐tumour properties of novel 4-substituted phthalazinones as Aurora B kinase inhibitors

  摘要：

  A series of novel 4-substituted phthalazinones as Aurora B kinase inhibitors was synthesized and evaluated the anti-proliferative activities against A549, HCT116, MCF-7 and HepG2 cells. 1-(4-(2-((4-Oxo-3,4-dihydrophthalazin-1-yl)amino)ethyl) phenyl)-3-(3-(trifluoromethyl)phenyl)urea (17b) exhibited the most potent anti-proliferative activity against HCT116 cells with IC50 value of 4.35 ± 1.21 μM, as well as the moderate Aurora B inhibitory activity with the IC50 value of 142 nM. Furthermore, 17b inhibited the phosphorylation of Aurora B on Thr232, leading to cell cycle arrest in the G2/M phase by down-regulating the expression of CyclinB1 and Cdc2 proteins, and apoptosis by up-regulating the expression of BAD and Bax proteins in HCT116 cells. In addition, a docking study revealed that 17b could form key hydrogen bonds with Ala173, Glu171 and Glu177 in Aurora B. All the results reveal that 17b is worthy of further development as an Aurora B kinase inhibitor.

  DOI：

  10.1016/j.bmcl.2020.127556
• 作为产物：
  描述：

  特定基氨基甲酸脂酶 在 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 N-(4-bromophthalazin-1-yl)benzene-1,4-diamine
  参考文献：
  名称：

  The synthesis and anti‐tumour properties of novel 4-substituted phthalazinones as Aurora B kinase inhibitors

  摘要：

  A series of novel 4-substituted phthalazinones as Aurora B kinase inhibitors was synthesized and evaluated the anti-proliferative activities against A549, HCT116, MCF-7 and HepG2 cells. 1-(4-(2-((4-Oxo-3,4-dihydrophthalazin-1-yl)amino)ethyl) phenyl)-3-(3-(trifluoromethyl)phenyl)urea (17b) exhibited the most potent anti-proliferative activity against HCT116 cells with IC50 value of 4.35 ± 1.21 μM, as well as the moderate Aurora B inhibitory activity with the IC50 value of 142 nM. Furthermore, 17b inhibited the phosphorylation of Aurora B on Thr232, leading to cell cycle arrest in the G2/M phase by down-regulating the expression of CyclinB1 and Cdc2 proteins, and apoptosis by up-regulating the expression of BAD and Bax proteins in HCT116 cells. In addition, a docking study revealed that 17b could form key hydrogen bonds with Ala173, Glu171 and Glu177 in Aurora B. All the results reveal that 17b is worthy of further development as an Aurora B kinase inhibitor.

  DOI：

  10.1016/j.bmcl.2020.127556

文献信息

• Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship
  作者：Rui Gao、Sha Liao、Chen Zhang、Weilong Zhu、Liyan Wang、Jin Huang、Zhenjiang Zhao、Honglin Li、Xuhong Qian、Yufang Xu

  DOI：10.1016/j.ejmech.2013.01.030

  日期：2013.4

  In this study, starting from a lead compound discovered by virtual screening, a series of novel hetero-cyclic substituted benzenesulfonamides were designed and synthesized as new carbonic anhydrase IX (CA IX) inhibitors. Some compounds exhibited potent inhibitory effects against CA IX (in the low nanomolar range) as well as high selectivity against other carbonic anhydrase isozymes (CA I and CA II). The most potent and selective compound 27 could inhibit CA IX in the subnanomolar level with IC50 of 0.48 nM, which increased the potency by about 40-fold against CA IX compared with the lead compound 26, and presented more than 10(3) fold selectivity over CA I and CA II. The structure activity relationship (SAR) based on the docking experiments further elucidated the effects of the compounds on the bioactivity and selectivity. (C) 2013 Elsevier Masson SAS. All rights reserved.
• The synthesis and anti‐tumour properties of novel 4-substituted phthalazinones as Aurora B kinase inhibitors
  作者：Xiu-Juan Zhang、Yu Xu、Hong-Xia Mou、Shuai Wang、Shu-Yi Hao、Shi-Wu Chen

  DOI：10.1016/j.bmcl.2020.127556

  日期：2020.12

  A series of novel 4-substituted phthalazinones as Aurora B kinase inhibitors was synthesized and evaluated the anti-proliferative activities against A549, HCT116, MCF-7 and HepG2 cells. 1-(4-(2-((4-Oxo-3,4-dihydrophthalazin-1-yl)amino)ethyl) phenyl)-3-(3-(trifluoromethyl)phenyl)urea (17b) exhibited the most potent anti-proliferative activity against HCT116 cells with IC50 value of 4.35 ± 1.21 μM, as well as the moderate Aurora B inhibitory activity with the IC50 value of 142 nM. Furthermore, 17b inhibited the phosphorylation of Aurora B on Thr232, leading to cell cycle arrest in the G2/M phase by down-regulating the expression of CyclinB1 and Cdc2 proteins, and apoptosis by up-regulating the expression of BAD and Bax proteins in HCT116 cells. In addition, a docking study revealed that 17b could form key hydrogen bonds with Ala173, Glu171 and Glu177 in Aurora B. All the results reveal that 17b is worthy of further development as an Aurora B kinase inhibitor.