(6-氯-嘧啶-4-基)-(3-三氟甲基-苯基)-胺 | 872510-82-2

• 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: (6-氯-嘧啶-4-基)-(3-三氟甲基-苯基)-胺
• 英文名称: (6-chloro-pyrimidin-4-yl)-(3-trifluoromethyl-phenyl)-amine
• 英文别名: (6-chloropyrimidin-4-yl)-(3-trifluoromethylphenyl)amine；6-Chloro-N-(3-(trifluoromethyl)phenyl)pyrimidin-4-amine；6-chloro-N-[3-(trifluoromethyl)phenyl]pyrimidin-4-amine
• CAS: 872510-82-2
• 化学式: C₁₁H₇ClF₃N₃
• mdl: MFCD10000669
• 分子量: 273.645
• InChiKey: PWQVXSLCVWMYTA-UHFFFAOYSA-N

物化性质

• 沸点：
  344.7±42.0 °C(Predicted)
• 密度：
  1.460±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (6-氯-嘧啶-4-基)-(3-三氟甲基-苯基)-胺 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 6-(4-{[4-(2-fluorobenzoyl)piperazin-1-yl]carbonyl}phenyl)-N-[3-(trifluoromethyl)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 、 间氨基三氟甲苯 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以77%的产率得到(6-氯-嘧啶-4-基)-(3-三氟甲基-苯基)-胺
  参考文献：
  名称：

  从组合激酶导向的杂环文库中发现 EGFR 选择性 4,6-二取代嘧啶

  摘要：

  表皮生长因子受体 (EGFR) 酪氨酸激酶是制药业开发药物的首批受体酪氨酸激酶之一，因为它在多种肿瘤中普遍存在过度表达。尽管在临床中验证了几种基于喹唑啉的支​​架，但仍缺乏能够选择性抑制 EGFR 激酶活性的替代化学结构类别。在这里，我们描述了酶促和细胞 EGFR 活性的强效和高选择性 4,6-二取代嘧啶抑制剂的发现，并解释了它们异常程度的激酶选择性。

  DOI：

  10.1021/ja0567485

文献信息

• [EN] PYRIMIDINE UREA DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DERIVES PYRIMIDINES UREE EN TANT QU'INHIBITEURS DE KINASE
  申请人：NOVARTIS AG

  公开号：WO2006000420A1

  公开（公告）日：2006-01-05

  The invention relates to compounds of formula (I) wherein the substituents X1, R1, R2, R3 and R4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, and a method for the treatment of such a disease.

  该发明涉及式(I)的化合物，其中取代基X1、R1、R2、R3和R4的含义如所述并解释在该发明的描述中，以及制备这些化合物的方法，含有相同化合物的药物组合物，可选择与一个或多个其他药用活性化合物结合使用，用于治疗对蛋白激酶活性抑制有反应的疾病，并且用于治疗此类疾病的方法。
• Compounds and compositions as protein kinase inhibitors
  申请人：Ding Qiang

  公开号：US08552002B2

  公开（公告）日：2013-10-08

  The invention relates to compounds of formula (I) wherein the substituents X1, R1, R2, R3 and R4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, and a method for the treatment of such a disease.

  本发明涉及公式（I）的化合物，其中取代基X1，R1，R2，R3和R4的含义如本发明说明书所述和解释的那样，以及制备这些化合物的过程，包含它们的药物组合物，可选地与一种或多种其他药物活性化合物结合使用以治疗对蛋白激酶活性抑制有反应的疾病，以及治疗这种疾病的方法。
• COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
  申请人：DING Qiang

  公开号：US20130012476A1

  公开（公告）日：2013-01-10

  The invention relates to compounds of formula (I) wherein the substituents X 1 , R 1 , R 2 , R 3 and R 4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, and a method for the treatment of such a disease.

  本发明涉及公式（I）的化合物，其中取代基X1、R1、R2、R3和R4的含义如发明说明中所述和解释的那样，以及制备这些化合物的方法、包含它们的药物组合物，其可选择与一个或多个其他药理活性化合物结合使用，用于治疗对蛋白激酶活性抑制有反应的疾病，以及用于治疗这种疾病的方法。
• Compounds and Compositions as Protein Kinase Inhibitors
  申请人：Ding Qiang

  公开号：US20090137804A1

  公开（公告）日：2009-05-28

  The invention relates to compounds of formula (I) wherein the substituents X 1 , R 1 , R 2 , R 3 and R 4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, and a method for the treatment of such a disease.

  本发明涉及公式（I）化合物，其中取代基X1，R1，R2，R3和R4的含义如本发明说明书所述和解释的那样，以及制备这些化合物的过程，包含它们的药物组合物，可选择与一种或多种其他药物活性化合物联合使用以治疗对蛋白激酶活性抑制有反应的疾病，以及治疗这种疾病的方法。
• Discovery and biological evaluation of 4,6-pyrimidine analogues with potential anticancer agents as novel colchicine binding site inhibitors
  作者：Jifa Zhang、Lun Tan、Chengyong Wu、Yuyan Li、Hao Chen、Yinghuan Liu、Yuxi Wang

  DOI：10.1016/j.ejmech.2022.115085

  日期：2023.2

  Novel 4,6-pyrimidine analogues were designed and synthesized as colchicine binding site inhibitors (CBSIs) with potent antiproliferative activities. Among them, compound 17j has the most potent activities against 6 human cancer cell lines with IC50 values from 1.1 nM to 4.4 nM, which was 76 times higher than the lead compound 3 in A549 cells. The co-crystal structure of 17j in complex with tubulin

  新型 4,6-嘧啶类似物被设计并合成为具有有效抗增殖活性的秋水仙碱结合位点抑制剂 (CBSI)。其中，化合物17j对6种人类癌细胞系的活性最强，IC 50值为1.1 nM至4.4 nM，是A549细胞中先导化合物3的76倍。与微管蛋白复合的17j的共晶结构证实了秋水仙碱结合位点的关键结合模式。此外，17j在生化测定中抑制微管蛋白聚合，解聚细胞微管，诱导 G2/M 停滞，抑制细胞迁移，促进细胞凋亡的启动。在体内，17j有效抑制原发性肿瘤生长，在 A549 异种移植模型中肿瘤生长抑制率为 42.51% (5 mg/kg) 和 65.42% (10 mg/kg)。总而言之，17j代表了有前途的新一代 CBSI。