2-ethyl-3-fluoro-4-(methylsulfonyl)benzoic acid | 1251164-94-9

• 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: 2-ethyl-3-fluoro-4-(methylsulfonyl)benzoic acid
• 英文别名: 2-ethyl-3-fluoro-4-methylsulfonylbenzoic acid
• CAS: 1251164-94-9
• 化学式: C₁₀H₁₁FO₄S
• 分子量: 246.259
• InChiKey: VTLHACMJXNPZKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-ethyl-3-fluoro-4-(methylsulfonyl)benzoic acid 、 7-(3H-benzimidazol-5-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine 在 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 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 7-(1H-benzimidazol-6-yl)-4-{[2-ethyl-3-fluoro-4-(methylsulfonyl)phenyl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepine
  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
• 作为产物：
  描述：

  1-Bromo-2-ethyl-3,4-difluorobenzene 在 Oxone 、 异丙基溴化镁 、 碳酸氢钠 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 丙酮 为溶剂， 反应 29.34h， 生成 2-ethyl-3-fluoro-4-(methylsulfonyl)benzoic acid
  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

• [EN] BENZOXAZEPIN-4- (5H) -YL DERIVATIVES AND THEIR USE TO TREAT CANCER<br/>[FR] DÉRIVÉS BENZOXAZEPIN-4-(5H)-YLE ET LEUR UTILISATION POUR TRAITER LE CANCER
  申请人：EXELIXIS INC

  公开号：WO2010118208A1

  公开（公告）日：2010-10-14

  The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

  这项发明涉及公式I的化合物及其药用可接受的盐或溶剂合物，以及制备和使用这些化合物的方法。
• Inhibitors of mTOR and Methods of Making and Using
  申请人：Anand Neel Kumar

  公开号：US20100305093A1

  公开（公告）日：2010-12-02

  The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

  本发明涉及公式I的化合物及其药学上可接受的盐或溶剂化物，以及制备和使用这些化合物的方法。
• 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.