6-chloro-N-(4-fluorophenyl)pyrimidin-4-amine

• 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: 6-chloro-N-(4-fluorophenyl)pyrimidin-4-amine
• 英文别名: 6-Chloro-N-(4-fluorophenyl)-4-pyrimidinamine
• 化学式: C₁₀H₇ClFN₃
• 分子量: 223.637
• InChiKey: XJMKBQFYZFRBAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 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：

  6-chloro-N-(4-fluorophenyl)pyrimidin-4-amine 在 四(三苯基膦)钯 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 72.17h， 生成 N-(4-fluorophenyl)-6-[4-({4-[3-(trifluoromethyl)benzoyl] piperazin-1-yl}carbonyl)phenyl]pyrimidin-4-amine
  参考文献：
  名称：

  Discovery of novel Bcr–Abl inhibitors targeting myristoyl pocket and ATP site

  摘要：

  Bcr-Abl plays an essential role in the pathogenesis and development of chronic myeloid leukaemia (CML). Inhibition of Bcr-Abl has great potential for therapeutic intervention in CML. In order to obtain novel and potent Bcr-Abl inhibitors, twenty seven 4,6-disubstituted pyrimidines were synthesized and evaluated herein. The biological results indicated that four compounds of them (C4, C5, C16, and C23) were potent Bcr-Abl inhibitors which were comparable to positive control. Moreover, C4 and C5 displayed promising antiproliferative activity against K562 cells. The results suggested that these 4, 6-disubstituted pyrimidines could serve as promising leads for further optimization of Bcr-Abl inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.030
• 作为产物：
  描述：

  4,6-二氯嘧啶 、 4-氟苯胺 在 potassium iodide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 6-chloro-N-(4-fluorophenyl)pyrimidin-4-amine
  参考文献：
  名称：

  N4，N6-二取代嘧啶-4,6-二胺衍生物作为有效的EGFR抑制剂在非小细胞肺癌中的设计，合成和药理评价

  摘要：

  设计，合成，评价了一系列新颖的4、6-二取代嘧啶衍生物，作为非小细胞肺癌（NSCLC）的表皮生长因子受体（EGFR）抑制剂。通过使用涉及支架跳跃的方法，利用4、6-二取代的嘧啶作为核心结构来取代喹唑啉基本骨架的前导结构AZD3759。结果发现，与AZD3759相比，化合物Yfq07在体外和体内均表现出最佳的抑制作用：Yfq07与AZD3759相比，它具有竞争性ATP抑制作用，多种目标作用，并且还具有更强的针对H3255，A431，HCC827，PC-9和H1975的活性。此外，还可以观察到更强的促凋亡作用，即抑制细胞G2 / M期对A431，H3255，HCC827和H1975的作用。在这项研究中，最终目标是改变核心结构，以改善其他表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的性能，同时保持整体效能。进一步探索了Yfq07作为一种有效的4，6-嘧啶类抗癌药，用于治疗人非小细胞肺癌。

  DOI：

  10.1016/j.ejmech.2018.08.031

文献信息

• Synthesis and biological evaluation of 4-(2-fluorophenoxy)-3,3′-bipyridine derivatives as potential c-met inhibitors
  作者：Sijia Zhao、Yu Zhang、Hongyang Zhou、Shuancheng Xi、Bin Zou、Guanglong Bao、Limei Wang、Jiao Wang、Tianfang Zeng、Ping Gong、Xin Zhai

  DOI：10.1016/j.ejmech.2016.04.062

  日期：2016.9

  Six series of novel 4-(2-fluorophenoxy)-3,3′-bipyridine derivatives conjugated with aza-aryl formamide/amine scaffords were designed and synthesized through a structure-based molecular hybridization approach. The target compounds were evaluated for c-Met kinase inhibitory activities and cytotoxicity against four cancer cell lines (HT-29, A549, MKN-45 and MDA-MB-231) in vitro. Most compounds exhibited

  通过基于结构的分子杂交方法，设计合成了六种新颖的与氮杂芳基甲酰胺/胺骨架共轭的4-（2-氟苯氧基）-3,3'-联吡啶衍生物。评估了目标化合物在体外对四种癌细胞系（HT-29，A549，MKN-45和MDA-MB-231）的c-Met激酶抑制活性和细胞毒性。大多数化合物均表现出中等至出色的效力，最有前途的候选蛋白26c（c-Met激酶IC 50  = 8.2 nM）在体外对c-Met上瘾的MKN-45细胞系的细胞毒性增加了4.7倍（IC 50  = 3 nM），优于Foretinib（IC 50 = 23 nM）。初步的结构-活性关系表明，1 H-苯并[e] [1,3,4]噻二嗪-3-羧酰胺-4,4-二氧化物部分作为连接基有助于抗肿瘤作用。
• TRK INHIBITION
  申请人：NantBio, Inc.

  公开号：US20180346451A1

  公开（公告）日：2018-12-06

  The present invention relates to the use of substituted pyrimidine derivatives to modulate tropomyosin-related kinase (Trk) family protein kinase, and the use of the substituted pyrimidine derivatives for the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

  本发明涉及使用取代嘧啶衍生物来调节肌球蛋白相关激酶（Trk）家族蛋白激酶，并且使用这些取代嘧啶衍生物来治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、牛皮癣、血栓形成、与失髓鞘或脱髓鞘相关的疾病、紊乱、损伤或功能障碍，或与神经生长因子（NGF）受体TrkA异常活动相关的疾病或紊乱。
• Trk inhibition
  申请人：NantBio, Inc.

  公开号：US10738033B2

  公开（公告）日：2020-08-11

  The present invention relates to the use of substituted pyrimidine derivatives to modulate tropomyosin-related kinase (Trk) family protein kinase, and the use of the substituted pyrimidine derivatives for the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA. The present invention also provides compounds of the formula: as defined herein.

  本发明涉及使用取代的嘧啶衍生物来调节肌球蛋白相关激酶（Trk）家族蛋白激酶，以及使用取代的嘧啶衍生物来治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、银屑病、血栓形成、与髓鞘脱落或脱髓鞘有关的疾病、失调、损伤或功能障碍，或与髓鞘异常活动有关的疾病或失调、 再狭窄、动脉粥样硬化、牛皮癣、血栓形成、与髓鞘脱落或脱髓鞘有关的疾病、紊乱、损伤或功能障碍，或与神经生长因子（NGF）受体 TrkA 的异常活动有关的疾病或紊乱。 本发明还提供了如本文所定义的式化合物。
• Design, synthesis and pharmacological evaluation of N4,N6-disubstituted pyrimidine-4,6-diamine derivatives as potent EGFR inhibitors in non-small cell lung cancer
  作者：Yuan Zhang、Handeng Lv、Lu Luo、Yong Xu、Yaqian Pan、Yuewu Wang、Han Lin、Jianhua Xiong、Ping Guo、Jinsan Zhang、Xiaokun Li、Faqing Ye

  DOI：10.1016/j.ejmech.2018.08.031

  日期：2018.9

  A novel series of 4, 6-disubstituted pyrimidines derivatives were designed, synthesized, and evaluated as epidermal growth factor receptor (EGFR) inhibitors for non-small cell lung cancer(NSCLC). 4, 6-disubstituted pyrimidines as core structure was utilized to substitute the lead structure AZD3759 of the quinazoline basic skeleton via an approach involving scaffold hopping. It was found that compound

  设计，合成，评价了一系列新颖的4、6-二取代嘧啶衍生物，作为非小细胞肺癌（NSCLC）的表皮生长因子受体（EGFR）抑制剂。通过使用涉及支架跳跃的方法，利用4、6-二取代的嘧啶作为核心结构来取代喹唑啉基本骨架的前导结构AZD3759。结果发现，与AZD3759相比，化合物Yfq07在体外和体内均表现出最佳的抑制作用：Yfq07与AZD3759相比，它具有竞争性ATP抑制作用，多种目标作用，并且还具有更强的针对H3255，A431，HCC827，PC-9和H1975的活性。此外，还可以观察到更强的促凋亡作用，即抑制细胞G2 / M期对A431，H3255，HCC827和H1975的作用。在这项研究中，最终目标是改变核心结构，以改善其他表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的性能，同时保持整体效能。进一步探索了Yfq07作为一种有效的4，6-嘧啶类抗癌药，用于治疗人非小细胞肺癌。
• Discovery of novel Bcr–Abl inhibitors targeting myristoyl pocket and ATP site
  作者：Jinyun Dong、Wen Lu、Xiaoyan Pan、Ping Su、Yaling Shi、Jinfeng Wang、Jie Zhang

  DOI：10.1016/j.bmc.2014.10.030

  日期：2014.12

  Bcr-Abl plays an essential role in the pathogenesis and development of chronic myeloid leukaemia (CML). Inhibition of Bcr-Abl has great potential for therapeutic intervention in CML. In order to obtain novel and potent Bcr-Abl inhibitors, twenty seven 4,6-disubstituted pyrimidines were synthesized and evaluated herein. The biological results indicated that four compounds of them (C4, C5, C16, and C23) were potent Bcr-Abl inhibitors which were comparable to positive control. Moreover, C4 and C5 displayed promising antiproliferative activity against K562 cells. The results suggested that these 4, 6-disubstituted pyrimidines could serve as promising leads for further optimization of Bcr-Abl inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.