1-(4-Aminophenyl)-3-[4-(trifluoromethyl)phenyl]urea | 1153359-22-8

• 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: 1-(4-Aminophenyl)-3-[4-(trifluoromethyl)phenyl]urea
• CAS: 1153359-22-8
• 化学式: C₁₄H₁₂F₃N₃O
• 分子量: 295.264
• InChiKey: QYXJQNQHVIIIPP-UHFFFAOYSA-N

物化性质

• 沸点：
  329.2±42.0 °C(predicted)
• 密度：
  1.435±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-Aminophenyl)-3-[4-(trifluoromethyl)phenyl]urea 、 4-氯-1H-吡唑并[3,4-d]嘧啶 在 盐酸 作用下， 以 水 、 正丁醇 为溶剂， 反应 3.83h， 以81%的产率得到1-[4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl]-3-[4-(trifluoromethyl)phenyl]urea
  参考文献：
  名称：

  Structure–Activity Relationship Studies of Pyrazolo[3,4-d]pyrimidine Derivatives Leading to the Discovery of a Novel Multikinase Inhibitor That Potently Inhibits FLT3 and VEGFR2 and Evaluation of Its Activity against Acute Myeloid Leukemia in Vitro and in Vivo

  摘要：

  We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo [3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis using cell- and transgenic-zebrafish-based assays led to the discovery of a number of compounds that exhibited both high potency against FLT3-driven human acute myeloid leukemia (AML) MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-based assays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (33), which exhibited the highest activity in preliminary in vivo anti-AML assays, was chosen for further anti AML studies. The results demonstrated that compound 33 is a multikinase inhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograft mouse model, a once daily dose of compound 33 at 10 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analyses were performed to determine the mechanism of action of compound 33.

  DOI：

  10.1021/jm301537p
• 作为产物：
  描述：

  4-(trifluoromethyl)-4'-nitrocarbanilide 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 生成 1-(4-Aminophenyl)-3-[4-(trifluoromethyl)phenyl]urea
  参考文献：
  名称：

  Structure–Activity Relationship Studies of Pyrazolo[3,4-d]pyrimidine Derivatives Leading to the Discovery of a Novel Multikinase Inhibitor That Potently Inhibits FLT3 and VEGFR2 and Evaluation of Its Activity against Acute Myeloid Leukemia in Vitro and in Vivo

  摘要：

  We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo [3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis using cell- and transgenic-zebrafish-based assays led to the discovery of a number of compounds that exhibited both high potency against FLT3-driven human acute myeloid leukemia (AML) MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-based assays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (33), which exhibited the highest activity in preliminary in vivo anti-AML assays, was chosen for further anti AML studies. The results demonstrated that compound 33 is a multikinase inhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograft mouse model, a once daily dose of compound 33 at 10 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analyses were performed to determine the mechanism of action of compound 33.

  DOI：

  10.1021/jm301537p

文献信息

• [EN] UREIDOPHENYL SUBSTITUTED TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS<br/>[FR] DÉRIVÉS DE LA TRIAZINE SUBSTITUÉE À L'URÉIDOPHÉNYLE ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：ABRAXIS BIOSCIENCE LLC

  公开号：WO2010144522A1

  公开（公告）日：2010-12-16

  The present invention provides Uredophenyl substituted triazine derivatives and provides methods of using these compounds to modulate protein kinases and methods of using these compounds to treat protein kinase mediated diseases and conditions.

  本发明提供了尿苯基取代的三嗪衍生物，并提供使用这些化合物调节蛋白激酶的方法，以及使用这些化合物治疗蛋白激酶介导的疾病和病状的方法。