4-[(2-氯-5-氟-4-嘧啶)氨基]-n-(2-氯苯基)苯甲酰胺 | 1158838-41-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[(2-氯-5-氟-4-嘧啶)氨基]-n-(2-氯苯基)苯甲酰胺
• 中文别名: 4-((2-氯-5-氟嘧啶-4-基)氨基)-N-(2-氯苯基)苯甲酰胺
• 英文名称: 4-((2-chloro-5-fluoropyrimidin-4-yl)amino)-N-(2-chlorophenyl)benzamide
• 英文别名: 4-(2-chloro-5-fluoropyrimidin-4-ylamino)-N-(2-chlorophenyl)benzamide；4-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-N-(2-chlorophenyl)benzamide
• CAS: 1158838-41-5
• 化学式: C₁₇H₁₁Cl₂FN₄O
• 分子量: 377.205
• InChiKey: YGMDVFGZSZSJNZ-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

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-[(2-氯-5-氟-4-嘧啶)氨基]-n-(2-氯苯基)苯甲酰胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 氘代二甲亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 tert-butyl 4-(2-(4-((4-((4-((2-chlorophenyl)carbamoyl)phenyl)amino)-5-fluoropyrimidin-2-yl)amino)phenyl)acetyl)piperazine-1-carboxylate
  参考文献：
  名称：

  AURKA 선택적 분해 유도 화합물

  摘要：

  本发明涉及一种能够诱导AURKA（ Aurora kinase A）选择性分解的新型化合物，具体来说，它是一种双功能化合物，其中包含与AURKA结合的基团和与E3泛素连接酶结合的基团，并且这两个基团通过化学连接基团相连。此外，本发明还提供这种化合物的制备方法及其用途。根据本发明的化合物在AURKA相关疾病的预防或治疗中具有应用价值。

  公开号：

  KR20240008889A
• 作为产物：
  描述：

  N-BOC-4-氨基苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 38.0h， 生成 4-[(2-氯-5-氟-4-嘧啶)氨基]-n-(2-氯苯基)苯甲酰胺
  参考文献：
  名称：

  Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors

  摘要：

  The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors.

  DOI：

  10.1016/j.bmc.2018.11.006

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.
• WO2022270987A1
  申请人：——

  公开号：WO2022270987A1

  公开（公告）日：2022-12-29
• 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.
• Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors
  作者：Chun-Yan Sang、Wen-Wen Qin、Xiu-Juan Zhang、Yu Xu、You-Zhen Ma、Xing-Rong Wang、Ling Hui、Shi-Wu Chen

  DOI：10.1016/j.bmc.2018.11.006

  日期：2019.1

  The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors.
• AURKA 선택적 분해 유도 화합물
  申请人：(주) 업테라

  公开号：KR20240008889A

  公开（公告）日：2024-01-19

  본 발명은 AURKA의 선택적 분해를 유도하는 신규 화합물에 관한 것으로, 구체적으로 AURKA 결합 모이어티와 E3 유비퀴틴 라이게이즈 결합 모이어티가 화학적 링커로 연결된 이기능성 화합물, 이의 제조방법, 및 이의 용도를 제공한다. 또한, 본 발명에 따른 화합물들은 AURKA 관련 질환의 예방 또는 치료에 유용하게 사용될 수 있다.

  本发明涉及一种能够诱导AURKA（ Aurora kinase A）选择性分解的新型化合物，具体来说，它是一种双功能化合物，其中包含与AURKA结合的基团和与E3泛素连接酶结合的基团，并且这两个基团通过化学连接基团相连。此外，本发明还提供这种化合物的制备方法及其用途。根据本发明的化合物在AURKA相关疾病的预防或治疗中具有应用价值。