2,2,2-trifluoro-1-[4-(7-phenyl-3,5-dihydro-2H-1,4-benzoxazepine-4-carbonyl)phenyl]ethanone | 1426385-45-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,2,2-trifluoro-1-[4-(7-phenyl-3,5-dihydro-2H-1,4-benzoxazepine-4-carbonyl)phenyl]ethanone
• CAS: 1426385-45-6
• 化学式: C₂₄H₁₈F₃NO₃
• 分子量: 425.407
• InChiKey: CTCFXGJHWAKIKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl 7-phenyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2,2,2-trifluoro-1-[4-(7-phenyl-3,5-dihydro-2H-1,4-benzoxazepine-4-carbonyl)phenyl]ethanone
  参考文献：
  名称：

  Discovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR)

  摘要：

  A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound 28 (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound 28 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.

  DOI：

  10.1021/jm3007933

文献信息

• Discovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR)
  作者：Craig S. Takeuchi、Byung Gyu Kim、Charles M. Blazey、Sunghoon Ma、Henry W. B. Johnson、Neel K. Anand、Arlyn Arcalas、Tae Gon Baik、Chris A. Buhr、Jonah Cannoy、Sergey Epshteyn、Anagha Joshi、Katherine Lara、Matthew S. Lee、Longcheng Wang、James W. Leahy、John M. Nuss、Naing Aay、Ron Aoyama、Paul Foster、Jae Lee、Isabelle Lehoux、Narsimha Munagala、Arthur Plonowski、Sharmila Rajan、John Woolfrey、Kyoko Yamaguchi、Peter Lamb、Nicole Miller

  DOI：10.1021/jm3007933

  日期：2013.3.28

  A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound 28 (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound 28 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.