N-[2-(dimethylamino)ethyl]-4-[({4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]phenyl}carbamoyl)amino]benzamide monotrifluoroacetate | 1202885-83-3

• 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: N-[2-(dimethylamino)ethyl]-4-[({4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]phenyl}carbamoyl)amino]benzamide monotrifluoroacetate
• 英文别名: N-[2-(dimethylamino)ethyl]-4-[[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)pyrrolo[2,3-d]pyrimidin-2-yl]phenyl]carbamoylamino]benzamide;2,2,2-trifluoroacetic acid
• CAS: 1202885-83-3
• 化学式: C₂HF₃O₂*C₃₀H₃₃F₃N₈O₃
• 分子量: 724.663
• InChiKey: QBCIIIZTECLSDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.07
• 重原子数：
  51
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  154
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  三氟乙酸 、 N,N-二甲基乙二胺 、 4-({[4-(7-(2,2,2-trifluoroethyl)-4-morpholin-4-yl-7H-pyrrolo-[2,3-d]pyrimidin-2-yl)phenyl]carbamoyl}amino)benzoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以99%的产率得到N-[2-(dimethylamino)ethyl]-4-[({4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]phenyl}carbamoyl)amino]benzamide monotrifluoroacetate
  参考文献：
  名称：

  Synthesis and SAR of Novel 4-Morpholinopyrrolopyrimidine Derivatives as Potent Phosphatidylinositol 3-Kinase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm901783v