6-[6-amino-5-[(2,6-dichloro-3-fluorophenyl)methoxy]-3-pyridyl]-1'-methylspiro[indoline-3,4'-piperidine]-2-one | 1253286-92-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-[6-amino-5-[(2,6-dichloro-3-fluorophenyl)methoxy]-3-pyridyl]-1'-methylspiro[indoline-3,4'-piperidine]-2-one
• 英文别名: 6-[6-amino-5-[(2,6-dichloro-3-fluorophenyl)methoxy]pyridin-3-yl]-1'-methylspiro[1H-indole-3,4'-piperidine]-2-one
• CAS: 1253286-92-8
• 化学式: C₂₅H₂₃Cl₂FN₄O₂
• 分子量: 501.388
• InChiKey: DXQPHTVBISVXGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-[(2,6-dichloro-3-fluorophenyl)methoxy]-2-nitropyridine 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 铁粉 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 、 乙腈 为溶剂， 反应 19.17h， 生成 6-[6-amino-5-[(2,6-dichloro-3-fluorophenyl)methoxy]-3-pyridyl]-1'-methylspiro[indoline-3,4'-piperidine]-2-one
  参考文献：
  名称：

  Aminopyridyl/Pyrazinyl Spiro[indoline-3,4′-piperidine]-2-ones As Highly Selective and Efficacious c-Met/ALK Inhibitors

  摘要：

  A series of novel aminopyridyl/pyrazinyl-substituted spiro[indoline-3,4'-piperidine]-2-ones were designed, synthesized, and tested in various in vitro/in vivo pharmacological and antitumor assays. 6-[6-Amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridyl]-1'-methylspiro[indoline-3,4'-piperidine]-2-one (compound 5b or SMU-B) was identified as a potent, highly selective, well-tolerated, and orally efficacious c-Met/ALK dual inhibitor, which showed pharmacodynamics effect by inhibiting c-Met phosphorylation in vivo and significant tumor growth inhibitions (>50%) in GTL-16 human gastric carcinoma xenograft models.

  DOI：

  10.1021/ml400203d

文献信息

• Aminopyridyl/Pyrazinyl Spiro[indoline-3,4′-piperidine]-2-ones As Highly Selective and Efficacious c-Met/ALK Inhibitors
  作者：Jingrong Li、Nan Wu、Yuanxin Tian、Jiajie Zhang、Shuguang Wu

  DOI：10.1021/ml400203d

  日期：2013.8.8

  A series of novel aminopyridyl/pyrazinyl-substituted spiro[indoline-3,4'-piperidine]-2-ones were designed, synthesized, and tested in various in vitro/in vivo pharmacological and antitumor assays. 6-[6-Amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridyl]-1'-methylspiro[indoline-3,4'-piperidine]-2-one (compound 5b or SMU-B) was identified as a potent, highly selective, well-tolerated, and orally efficacious c-Met/ALK dual inhibitor, which showed pharmacodynamics effect by inhibiting c-Met phosphorylation in vivo and significant tumor growth inhibitions (>50%) in GTL-16 human gastric carcinoma xenograft models.