2-chloro-4-(o-chloroanilino)-5-nitropyrimidine

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-chloro-4-(o-chloroanilino)-5-nitropyrimidine
• 英文别名: 2-chloro-N-(2-chlorophenyl)-5-nitropyrimidin-4-amine
• 化学式: C₁₀H₆Cl₂N₄O₂
• 分子量: 285.089
• InChiKey: JKHZQDKQLLVCJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 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：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(o-chloroanilino)-5-nitropyrimidine 在 氯化铵 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 、 异丙醇 为溶剂， 生成
  参考文献：
  名称：

  的发现选择性EGFR调节剂抑制L858R / T790M双突变体带有N- 9-二苯基-9- ħ -嘌呤-2-胺骨架

  摘要：

  根据市售的AZD9291与T790M的模型结合模式，设计并合成了一系列N -9-联苯-9 H-嘌呤-2-胺衍生物，目的是克服T790M / L858R双突变引起的耐药性。最有效的化合物23a对单T790M和双T790M / L858R突变EGFR均表现出优异的酶抑制活性和选择性，纳摩尔IC 50值为50，对野生型EGFR的选择性超过8倍。化合物23a展示了对带有T790M / L858R的H1975非小细胞肺癌（NSCLC）细胞的强抗增殖活性。而且它对A549细胞（WT EGFR和k-Ras突变）和HT-29细胞（非特殊基因类型）的效力较弱，显示出较高的安全指数。

  DOI：

  10.1016/j.bmc.2018.02.029
• 作为产物：
  描述：

  tert-butyl (4-((2-chlorophenyl)carbamoyl)phenyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 2-chloro-4-(o-chloroanilino)-5-nitropyrimidine
  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

• 一种极光激酶A抑制剂及其制备与应用
  申请人：兰州大学

  公开号：CN106674197A

  公开（公告）日：2017-05-17

  本发明公开一种新型稳定氮氧自由基标记的极光激酶A抑制剂，以及这种抑制剂的制备方法和用途。本发明的抑制剂是N-(5-氟-4-邻氯苯胺-嘧啶-2)-氨基苯甲酸4-氨基-2,2,6,6-四甲基哌啶氮氧化物酰胺，或N-5-氟-4-氨基-(苯甲酰邻氯苯胺)-嘧啶-2}-氨基苯甲酸4-氨基-2,2,6,6-四甲基哌啶氮氧化物酰胺。本发明的方法是由2,4-二氯-5-取代-嘧啶依次与苯胺，或对氨基苯甲酰苯胺，和4-氨基-2,2,6,6-四甲基哌啶氮氧化物发生取代反应制备目标化合物。本发明的用途是将所述的化合物用于制备抗癌药物。
• 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.
• Discovery of selective EGFR modulator to inhibit L858R/T790M double mutants bearing a N-9-Diphenyl-9H-purin-2-amine scaffold
  作者：Jinxing Hu、Yufei Han、Jingtao Wang、Yue Liu、Yanfang Zhao、Yajing Liu、Ping Gong

  DOI：10.1016/j.bmc.2018.02.029

  日期：2018.5

  resistance resulted from T790M/L858R double mutations. The most potent compound 23a showed excellent enzyme inhibitory activities and selectivity with nanomolar IC50 values for both the single T790M and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 23a displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells

  根据市售的AZD9291与T790M的模型结合模式，设计并合成了一系列N -9-联苯-9 H-嘌呤-2-胺衍生物，目的是克服T790M / L858R双突变引起的耐药性。最有效的化合物23a对单T790M和双T790M / L858R突变EGFR均表现出优异的酶抑制活性和选择性，纳摩尔IC 50值为50，对野生型EGFR的选择性超过8倍。化合物23a展示了对带有T790M / L858R的H1975非小细胞肺癌（NSCLC）细胞的强抗增殖活性。而且它对A549细胞（WT EGFR和k-Ras突变）和HT-29细胞（非特殊基因类型）的效力较弱，显示出较高的安全指数。