2-chloro-N-(4-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)benzamide | 1158838-39-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-N-(4-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)benzamide
• 英文别名: 2-chloro-N-[4-[(2-chloro-5-fluoropyrimidin-4-yl)amino]phenyl]benzamide
• CAS: 1158838-39-1
• 化学式: C₁₇H₁₁Cl₂FN₄O
• 分子量: 377.205
• InChiKey: DBIGRMMODLRPOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)benzamide 在 对甲苯磺酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成
  参考文献：
  名称：

  2,4-DIANILINOPYRIMIDINE-BASED AURORA-A KINASE SELECTIVE DEGRADATION INDUCING COMPOUNDS

  摘要：

  Novel 2,4-Dianilinopyrimidine-based Aurora-A kinase (AURKA) degraders are disclosed. The present AURKA degraders are proteolysis targeting chimeras (PROTACs) that recruit AURKA protein into optimized CRBN E3 ubiquitin ligase via linkers. The compounds may induce selective AURKA degradation and may be utilized for the treatment of cancer.

  公开号：

  WO2024155112A1
• 作为产物：
  描述：

  邻氯苯甲酰氯 在 铁粉 、 氯化铵 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 52.0h， 生成 2-chloro-N-(4-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)benzamide
  参考文献：
  名称：

  2,4-DIANILINOPYRIMIDINE-BASED AURORA-A KINASE SELECTIVE DEGRADATION INDUCING COMPOUNDS

  摘要：

  Novel 2,4-Dianilinopyrimidine-based Aurora-A kinase (AURKA) degraders are disclosed. The present AURKA degraders are proteolysis targeting chimeras (PROTACs) that recruit AURKA protein into optimized CRBN E3 ubiquitin ligase via linkers. The compounds may induce selective AURKA degradation and may be utilized for the treatment of cancer.

  公开号：

  WO2024155112A1

文献信息

• A Class of 2,4-Bisanilinopyrimidine Aurora A Inhibitors with Unusually High Selectivity against Aurora B
  作者：Ignacio Aliagas-Martin、Dan Burdick、Laura Corson、Jennafer Dotson、Jason Drummond、Carter Fields、Oscar W. Huang、Thomas Hunsaker、Tracy Kleinheinz、Elaine Krueger、Jun Liang、John Moffat、Gail Phillips、Rebecca Pulk、Thomas E. Rawson、Mark Ultsch、Leslie Walker、Christian Wiesmann、Birong Zhang、Bing-Yan Zhu、Andrea G. Cochran

  DOI：10.1021/jm9000314

  日期：2009.5.28

  The two major Aurora kinases carry out critical functions at distinct mitotic stages. Selective inhibitors of these kinases, as well as pan-Aurora inhibitors, show antitumor efficacy and are now under clinical investigation. However, the ATP-binding sites of Aurora A and Aurora B are virtually identical, and the structural basis for selective inhibition has therefore not been clear. We report here a class of bisanilinopyrimidine Aurora A inhibitors with excellent selectivity for Aurora A over Aurora B, both in enzymatic assays and in cellular phenotypic assays. Crystal structures of two of the inhibitors in complex with Aurora A implicate a single amino acid difference in Aurora B as responsible for poor inhibitory activity against this enzyme. Mutation of this residue in Aurora B (E161T) or Aurora A (T217E) is sufficient to swap the inhibition profile, suggesting that this difference might be exploited more generally to achieve high selectivity for Aurora A.
• 2,4-DIANILINOPYRIMIDINE-BASED AURORA-A KINASE SELECTIVE DEGRADATION INDUCING COMPOUNDS
  申请人：[en]UPPTHERA, INC.

  公开号：WO2024155112A1

  公开（公告）日：2024-07-25

  Novel 2,4-Dianilinopyrimidine-based Aurora-A kinase (AURKA) degraders are disclosed. The present AURKA degraders are proteolysis targeting chimeras (PROTACs) that recruit AURKA protein into optimized CRBN E3 ubiquitin ligase via linkers. The compounds may induce selective AURKA degradation and may be utilized for the treatment of cancer.