4-((4-bromophthalazin-1-yl)amino)benzenesulfonamide | 1402423-55-5

• 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: 4-((4-bromophthalazin-1-yl)amino)benzenesulfonamide
• 英文别名: 4-[(4-Bromophthalazin-1-yl)amino]benzenesulfonamide；4-[(4-bromophthalazin-1-yl)amino]benzenesulfonamide
• CAS: 1402423-55-5
• 化学式: C₁₄H₁₁BrN₄O₂S
• 分子量: 379.237
• InChiKey: KRFRQQKGCAOLDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((4-bromophthalazin-1-yl)amino)benzenesulfonamide 、 苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 4.0h， 以33%的产率得到4-((4-phenylphthalazin-1-yl)amino)benzenesulfonamide
  参考文献：
  名称：

  Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.01.030
• 作为产物：
  描述：

  邻苯二甲酰肼 在 potassium carbonate 、 三溴氧磷 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 4-((4-bromophthalazin-1-yl)amino)benzenesulfonamide
  参考文献：
  名称：

  Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.01.030

文献信息

• Discovery of potent nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) inhibitors with ancillary carbonic anhydrase inhibition for cancer (immuno)therapy
  作者：Sang-Yong Lee、Vigneshwaran Namasivayam、Nader M. Boshta、Arianna Perotti、Salahuddin Mirza、Silvia Bua、Claudiu T. Supuran、Christa E. Müller

  DOI：10.1039/d1md00117e

  日期：——

  inhibitor of human NPP3 identified by compound library screening. Subsequent structure–activity relationship (SAR) studies led to the potent competitive NPP3 inhibitor 2-methyl-5-4-[(4-sulfamoylphenyl)amino]phthalazin-1-yl}benzenesulfonamide (23, Ki 53.7 nM versus the natural substrate ATP). Docking studies predicted its binding pose and interactions. While 23 displayed high selectivity versus other ecto-nucleotidases

  核苷酸焦磷酸酶/磷酸二酯酶3 (NPP3) 催化细胞外核苷酸的水解。它由免疫细胞和一些癌症（例如肾癌和结肠癌）表达。 NPP3 与 5′-核苷酸酶 (CD73) 一起产生免疫抑制、促进癌症的腺苷，因此被提议作为癌症治疗的靶点。在此，我们报告通过化合物库筛选发现 4-[(4-甲基酞嗪-1-基)氨基]苯磺酰胺 ( 1 ) 作为人 NPP3 抑制剂。随后的构效关系 (SAR) 研究发现了有效的竞争性 NPP3 抑制剂 2-甲基-5-4-[(4-氨磺酰基苯基)氨基]酞嗪-1-基}苯磺酰胺（ 23 ， K i 53.7 nM，与天然药物相比）底物 ATP）。对接研究预测了它的结合姿势和相互作用。虽然23与其他核酸外切酶相比表现出高选择性，但它对两个拟议的抗癌靶点碳酸酐酶 CA-II (K i 74.7 nM) 和 CA-IX (K i 20.3 nM) 表现出辅助抑制作用。因此， 23可能作为多靶点抗癌药物。
• 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.