N-[2-(dimethylamino)ethyl]-N-methyl-4-{[(3-oxo-2,3-dihydro-1-benzofuran-5-yl)carbamoyl]amino}benzamide trifluoroacetate | 1200538-36-8

• 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: N-[2-(dimethylamino)ethyl]-N-methyl-4-{[(3-oxo-2,3-dihydro-1-benzofuran-5-yl)carbamoyl]amino}benzamide trifluoroacetate
• 英文别名: N-(2-(dimethylamino)ethyl)-N-methyl-4-(3-(3-oxo-2,3-dihydrobenzofuran-5-yl)ureido)benzamide TFA salt；N-[2-(dimethylamino)ethyl]-N-methyl-4-[(3-oxo-1-benzofuran-5-yl)carbamoylamino]benzamide;2,2,2-trifluoroacetic acid
• CAS: 1200538-36-8
• 化学式: C₂HF₃O₂*C₂₁H₂₄N₄O₄
• 分子量: 510.47
• InChiKey: VECRLPMFCLQHEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-[2-(dimethylamino)ethyl]-N-methyl-4-{[(3-oxo-2,3-dihydro-1-benzofuran-5-yl)carbamoyl]amino}benzamide trifluoroacetate 、 7-fluoro-5-methoxy-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indole-3-carbaldehyde 在 三氟乙酸 作用下， 以 盐酸 、 乙醇 为溶剂， 反应 18.0h， 以to give N-[2-(dimethylamino)ethyl]-4-({[(2Z)-2-{[7-fluoro-5-methoxy-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indol-3-yl]methylidene}-3-oxo-2,3-dihydro-1-benzofuran-5-yl]carbamoyl}amino)-N-methylbenzamide TFA salt (1.58 g, 1.931 mmol, 41.1%) as an orange solid的产率得到(Z)-N-(2-(dimethylamino)ethyl)-4-(3-(2-((7-fluoro-5-methoxy-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-5-yl)ureido)-N-methylbenzamide trifluoroacetate
  参考文献：
  名称：

  3-SUBSTITUTED-1H-INDOLE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

  摘要：

  本发明涉及以下式子的3-取代-1H-吲哚化合物I：或其药学上可接受的盐，其中组成变量如本文所定义，包括该化合物的组合物和制备和使用该化合物的方法。

  公开号：

  US20090311217A1
• 作为产物：
  描述：

  4-氨基-n-(2-(二甲基氨基)乙基)-n-甲基苯甲酰胺 、 三光气 、 5-aminobenzofuran-3(2H)-one 、 三氟乙酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以37.4%的产率得到N-[2-(dimethylamino)ethyl]-N-methyl-4-{[(3-oxo-2,3-dihydro-1-benzofuran-5-yl)carbamoyl]amino}benzamide trifluoroacetate
  参考文献：
  名称：

  5-Ureidobenzofuranone indoles as potent and efficacious inhibitors of PI3 kinase-α and mTOR for the treatment of breast cancer

  摘要：

  A series of 5-ureidobenzofuran-3-one indoles as potent inhibitors of PI3K alpha and mTOR has been developed. The best potency in cells was obtained when the urea group was extended to a 4-[2-(dimethylamino)ethyl]methylamino amidophenyl group. A 7-fluoro group on the indole ring also enhanced cellular potency. Compound 18i, incorporating the optimal functional groups, showed high potency in cellular lines and was further studied in vivo. It was able to inhibit the biomarker phosphorylation for 8 h when dosed at 25 mg/kg iv. In the MDA-MB-361 breast cancer model, it shrank the tumor size remarkably when dosed at 25 mg/kg iv on days 1, 5, and 9. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.139

文献信息

• 3-SUBSTITUTED-1H-INDOLE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
  申请人：Bursavich Matthew Gregory

  公开号：US20090311217A1

  公开（公告）日：2009-12-17

  The invention relates to 3-substituted-1H-indole 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.

  本发明涉及以下式子的3-取代-1H-吲哚化合物I：或其药学上可接受的盐，其中组成变量如本文所定义，包括该化合物的组合物和制备和使用该化合物的方法。
• 5-Ureidobenzofuranone indoles as potent and efficacious inhibitors of PI3 kinase-α and mTOR for the treatment of breast cancer
  作者：Nan Zhang、Semiramis Ayral-Kaloustian、James T. Anderson、Thai Nguyen、Sasmita Das、Aranapakam M. Venkatesan、Natasja Brooijmans、Judy Lucas、Ker Yu、Irwin Hollander、Robert Mallon

  DOI：10.1016/j.bmcl.2010.04.139

  日期：2010.6

  A series of 5-ureidobenzofuran-3-one indoles as potent inhibitors of PI3K alpha and mTOR has been developed. The best potency in cells was obtained when the urea group was extended to a 4-[2-(dimethylamino)ethyl]methylamino amidophenyl group. A 7-fluoro group on the indole ring also enhanced cellular potency. Compound 18i, incorporating the optimal functional groups, showed high potency in cellular lines and was further studied in vivo. It was able to inhibit the biomarker phosphorylation for 8 h when dosed at 25 mg/kg iv. In the MDA-MB-361 breast cancer model, it shrank the tumor size remarkably when dosed at 25 mg/kg iv on days 1, 5, and 9. (C) 2010 Elsevier Ltd. All rights reserved.