4-({[4-(7-(2,2,2-trifluoroethyl)-4-morpholin-4-yl-7H-pyrrolo-[2,3-d]pyrimidin-2-yl)phenyl]carbamoyl}amino)benzoic acid | 1202885-81-1

• 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: 4-({[4-(7-(2,2,2-trifluoroethyl)-4-morpholin-4-yl-7H-pyrrolo-[2,3-d]pyrimidin-2-yl)phenyl]carbamoyl}amino)benzoic acid
• 英文别名: 4-({[4-(7-(2,2,2-trifluoroethyl)-4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)phenyl]carbamoyl}amino)benzoic Acid；4-[[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)pyrrolo[2,3-d]pyrimidin-2-yl]phenyl]carbamoylamino]benzoic acid
• CAS: 1202885-81-1
• 化学式: C₂₆H₂₃F₃N₆O₄
• 分子量: 540.502
• InChiKey: XUYFRSQPTYWIAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-({[4-(7-(2,2,2-trifluoroethyl)-4-morpholin-4-yl-7H-pyrrolo-[2,3-d]pyrimidin-2-yl)phenyl]carbamoyl}amino)benzoic acid 、 2,2-二甲基哌嗪 以gave the title compound as off-white solid (1TFA salt, 21.3 mg, 47% yield)的产率得到1-{4-[(3,3-dimethylpiperazin-1-yl)carbonyl]phenyl}-3-{4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]phenyl}urea
  参考文献：
  名称：

  (2-ARYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)MORPHOLINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

  摘要：

  本发明涉及式I的2-芳基-7H-吡咯并[2,3-d]嘧啶-4-基)吗啡啶化合物或其药学上可接受的盐，其中组成变量如本文所定义，包含该化合物的组合物以及制备和使用该化合物的方法。

  公开号：

  US20100003250A1
• 作为产物：
  描述：

  methyl 4-[({4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo-[2,3-d]pyrimidin-2-yl]phenyl}carbamoyl)amino]benzoate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以100%的产率得到4-({[4-(7-(2,2,2-trifluoroethyl)-4-morpholin-4-yl-7H-pyrrolo-[2,3-d]pyrimidin-2-yl)phenyl]carbamoyl}amino)benzoic acid
  参考文献：
  名称：

  (2-ARYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)MORPHOLINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

  摘要：

  这项发明涉及Formula I的2-芳基-7H-吡咯并[2,3-d]嘧啶-4-基)吗啉化合物或其药用可接受的盐，其中组分变量如本文所定义，包括这些化合物的组合物，以及制备和使用这些化合物的方法。

  公开号：

  US20100003250A1

文献信息

• (2-ARYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)MORPHOLINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
  申请人：Chen Zecheng

  公开号：US20100003250A1

  公开（公告）日：2010-01-07

  The invention relates to 2-aryl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine compounds of the Formula I: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  这项发明涉及Formula I的2-芳基-7H-吡咯并[2,3-d]嘧啶-4-基)吗啉化合物或其药用可接受的盐，其中组分变量如本文所定义，包括这些化合物的组合物，以及制备和使用这些化合物的方法。
• Synthesis and SAR of Novel 4-Morpholinopyrrolopyrimidine Derivatives as Potent Phosphatidylinositol 3-Kinase Inhibitors
  作者：Zecheng Chen、Aranapakam M. Venkatesan、Christoph M. Dehnhardt、Semiramis Ayral-Kaloustian、Natasja Brooijmans、Robert Mallon、Larry Feldberg、Irwin Hollander、Judy Lucas、Ker Yu、Fangming Kong、Tarek S. Mansour

  DOI：10.1021/jm901783v

  日期：2010.4.22

  Significant evidence suggests that deregulation of the PI3K/Akt pathway is important in tumor progression. Mechanisms include loss of function of the tumor suppressor PTEN and high frequency of mutation of the PI3K p110 alpha isoform in human malignancies. This connection between PI3K and tumor genesis makes PI3K a promising target for cancer treatment. A series of 4-morpholinopyrrolopyrimidine derivatives were synthesized and evaluated as inhibitors of PI3K alpha and mTOR, leading to the discovery of PI3K alpha selective inhibitors (e.g., 9) and dual PI3K alpha/mTOR kinase inhibitors (e.g., 46 and 48). PI3K alpha/mTOR dual inhibitors demonstrated inhibition of tumor cell growth in vitro and in vivo and caused suppression of the pathway specific biomarkers [e.g., the phosphorylation of Akt at Thr308 (T308) and Ser473 (S473)] in the human breast cancer cell line MDA361. In addition, compound 46 demonstrated good in vivo efficacy in the MDA361 human breast tumor xenograft model.