2-chloro-N-(2-chlorophenyl)-5-fluoropyrimidin-4-amine | 1395918-39-4

• 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-(2-chlorophenyl)-5-fluoropyrimidin-4-amine
• CAS: 1395918-39-4
• 化学式: C₁₀H₆Cl₂FN₃
• 分子量: 258.082
• InChiKey: FUGQGVDORDCAHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(2-chlorophenyl)-5-fluoropyrimidin-4-amine 在 盐酸 、 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 48.5h， 生成 4-((4-((2-chlorophenyl)amino)-5-fluoropyrimidin-2-yl)amino)-N-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)ethyl)piperidin-1-yl)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
• 作为产物：
  描述：

  邻氯苯胺 、 2,4-二氯-5-氟嘧啶 在 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以76%的产率得到2-chloro-N-(2-chlorophenyl)-5-fluoropyrimidin-4-amine
  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

• AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
  申请人：Sebti Said M.

  公开号：US20140057913A1

  公开（公告）日：2014-02-27

  Described herein are inhibitors of Aurora kinase and their use in the treatment of cancer. Methods of screening for selective inhibitors of Aurora kinases are also disclosed.

  本文描述了Aurora激酶的抑制剂及其在癌症治疗中的应用。还公开了筛选选择性抑制Aurora激酶的方法。
• [EN] AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF<br/>[FR] INHIBITEURS DE KINASE AURORA ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER
  申请人：H LEE MOFFITT CANCER CT AND RES INST

  公开号：WO2012135641A3

  公开（公告）日：2012-12-27
• Development of <i>o</i>-Chlorophenyl Substituted Pyrimidines as Exceptionally Potent Aurora Kinase Inhibitors
  作者：Harshani R. Lawrence、Mathew P. Martin、Yunting Luo、Roberta Pireddu、Hua Yang、Harsukh Gevariya、Sevil Ozcan、Jin-Yi Zhu、Robert Kendig、Mercedes Rodriguez、Roy Elias、Jin Q. Cheng、Saïd M. Sebti、Ernst Schonbrunn、Nicholas J. Lawrence

  DOI：10.1021/jm300334d

  日期：2012.9.13

  The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC50 = 6.1 +/- 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallography studies revealed that compound 1 is a type I inhibitor that binds the Aurora kinase active site in a DFG-in conformation. Structure-activity guided replacement of the A-ring carboxylic acid with halogens and incorporation of fluorine at the pyrimidine 5-position led to highly potent inhibitors of Aurora A that bind in a DFG-out conformation. B-Ring modifications were undertaken to improve the solubility and cell permeability. Compounds such as 9m with water-solubilizing moieties at the para position of the B-ring inhibited the autophosphorylation of Aurora A in MDA-MB-468 breast cancer cells.
• US9249124B2
  申请人：——

  公开号：US9249124B2

  公开（公告）日：2016-02-02
• US9597329B2
  申请人：——

  公开号：US9597329B2

  公开（公告）日：2017-03-21