2-chloro-4-(4-nitro-phenoxy)-pyrimidine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-(4-nitro-phenoxy)-pyrimidine
• 英文别名: 2-Chloro-4-(4-nitrophenoxy)pyrimidine
• 化学式: C₁₀H₆ClN₃O₃
• mdl: MFCD17932638
• 分子量: 251.629
• InChiKey: SVFZOGUHNLYZIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 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：
  80.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(4-nitro-phenoxy)-pyrimidine 在 ammonium hydroxide 、 氢气 作用下， 生成 4-(4-氨基苯氧基)嘧啶-2-胺
  参考文献：
  名称：

  Flt3激酶抑制剂三联体的合成：从试验台到试验工厂†

  摘要：

  我们已经设计和开发了一种替代合成方法，用于生产Flt3激酶抑制剂三联体（AST487，ATH686和AUZ454），以支持对Flt3依赖性肿瘤疾病患者的临床评估。新的合成方法具有收敛性，环境友好性，实用性和安全性，并且不需要色谱纯化。

  DOI：

  10.1021/op800136f
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 对硝基苯酚 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 生成 2-chloro-4-(4-nitro-phenoxy)-pyrimidine
  参考文献：
  名称：

  联苯脲衍生物作为VEGFR-2激酶抑制剂的设计，合成和生物学评估（II）

  摘要：

  抑制VEGFR-2信号通路是最有前途的癌症治疗方法之一。在本文中，我们报道了一系列作为VEGFR-2抑制剂的联苯脲衍生物的设计，合成和生物学评估。在这些化合物中，有39种在体外和体内均表现出对VEGFR-2的有效抑制活性。管形成试验和鸡绒膜尿囊膜试验均进一步证实了39的抗血管生成活性。

  DOI：

  10.1016/j.cclet.2015.10.004

文献信息

• Diaryl urea derivatives useful for the treatment of protein kinase dependent diseases
  申请人：Floersheimer Andreas

  公开号：US20060128734A1

  公开（公告）日：2006-06-15

  The invention relates to the use of diaryl urea derivatives in the treatment of protein kinase dependent diseases or for the manufacture of pharmaceutical compositions for use in the treatment of said diseases, methods of use of diaryl urea derivatives in the treatment of said diseases, pharmaceutical preparations comprising diaryl urea derivatives for the treatment of said diseases, diaryl urea derivatives for use in the treatment of said diseases, novel diaryl urea derivatives, pharmaceutical preparations comprising these novel diaryl urea derivatives, processes for the manufacture of the novel diaryl urea derivatives, the use or methods of use of the novel diaryl urea derivatives as mentioned above, and/or these novel diaryl urea derivatives for use in the treatment of the animal or human body.

  本发明涉及在蛋白激酶依赖性疾病的治疗中使用二芳基脲衍生物或用于制造用于治疗该类疾病的药物组合物，二芳基脲衍生物在治疗该类疾病中的使用方法，包含二芳基脲衍生物的制备用于治疗该类疾病的制药制剂，用于治疗该类疾病的二芳基脲衍生物，新型的二芳基脲衍生物，包含这些新型二芳基脲衍生物的制药制剂，制造这些新型二芳基脲衍生物的方法，上述新型二芳基脲衍生物的使用或使用方法，以及/或这些新型二芳基脲衍生物用于治疗动物或人体。
• Diaryl Urea Derivatives in the Treatment of Protein Kinase Dependent Diseases
  申请人：Bold Guido

  公开号：US20080312192A1

  公开（公告）日：2008-12-18

  The invention relates to the use of diaryl urea derivatives for the manufacture of pharmaceutical compositions for the treatment of RET dependent disorders, especially RET dependent tumour diseases. The invention further relates to novel N-[4-(pyrimidin-4-yloxy)-phenyl]-N′-phenyl-urea derivatives and their use in the treatment of the animal or human body, especially in the treatment of a protein kinase dependent disease, to pharmaceutical compositions comprising such novel N-[4-(pyrimidin-4-yloxy)-phenyl]-N′-phenyl-urea derivatives and to the use of such novel N-[4-(pyrimidin-4-yloxy)-phenyl]-N′-phenyl-urea derivatives for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as tumour diseases.

  本发明涉及利用二芳基脲衍生物制造药物组合物，用于治疗RET依赖性疾病，特别是RET依赖性肿瘤疾病。本发明还涉及新的N-[4-(嘧啶-4-氧基)-苯基]-N'-苯基脲衍生物及其在动物或人体内治疗蛋白激酶依赖性疾病，特别是增殖性疾病，如肿瘤疾病方面的用途。此外，本发明还涉及包含这种新的N-[4-(嘧啶-4-氧基)-苯基]-N'-苯基脲衍生物的药物组合物，以及利用这种新的N-[4-(嘧啶-4-氧基)-苯基]-N'-苯基脲衍生物制备用于治疗蛋白激酶依赖性疾病，特别是增殖性疾病，如肿瘤疾病的药物组合物的用途。
• [EN] DIARYL UREA DERIVATIVES IN THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES<br/>[FR] DERIVES DE DIARYLUREE UTILISES EN TRAITEMENT DE MALADIES DEPENDANT DE PROTEINES KINASES
  申请人：NOVARTIS AG

  公开号：WO2005051366A3

  公开（公告）日：2007-12-21
• [EN] DIARYL UREA DERIVATIVES USEFUL FOR THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES<br/>[FR] DERIVES DE DIARYLE-UREE UTILISES POUR LE TRAITEMENT DES MALADIES DEPENDANT DES PROTEINES KINASES
  申请人：——

  公开号：WO2003099771A3

  公开（公告）日：2004-04-01
• Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity
  作者：Zhengsheng Zhan、Jing Ai、Qiufeng Liu、Yinchun Ji、Tiantian Chen、Yechun Xu、Meiyu Geng、Wenhu Duan

  DOI：10.1021/ml500066m

  日期：2014.6.12

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.