ethyl 4-(4-(tert-butoxycarbonyl)amino-3-fluorophenoxy)-2-aminopyridin-3-yl-carbamate | 1160825-89-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-(4-(tert-butoxycarbonyl)amino-3-fluorophenoxy)-2-aminopyridin-3-yl-carbamate
• 英文别名: ethyl 4-(4-N-(tert-butoxycarbonyl)-amino-3-fluorophenoxy)-2-aminopyridin-3-yl-carbamate；N-[2-amino-4-[4-[[(1,1-dimethylethoxy)carbonyl]amino]-3-fluorophenoxy]-3-pyridinyl]carbamic acid ethyl ester；tert-butyl N-[4-[2-amino-3-(ethoxycarbonylamino)pyridin-4-yl]oxy-2-fluorophenyl]carbamate
• CAS: 1160825-89-7
• 化学式: C₁₉H₂₃FN₄O₅
• 分子量: 406.414
• InChiKey: OAWAEWDOYZORPH-UHFFFAOYSA-N

物化性质

• 沸点：
  441.0±45.0 °C(Predicted)
• 密度：
  1.333±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-(tert-butoxycarbonyl)amino-3-fluorophenoxy)-2-aminopyridin-3-yl-carbamate 在 sodium ethanolate 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 甲苯 、 mineral oil 为溶剂， 反应 36.67h， 生成 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-fluoro-4-(1-N-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)urea
  参考文献：
  名称：

  [EN] 1-(5-TERT-BUTYL-2-PHENYL-2H-PYRAZOL-3-YL)-3-[2-FLUORO-4-(1-METHYL-2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-7-YLOXY)-PHENYL]-UREA AND RELATED COMPOUNDS AND THEIR USE IN THERAPY
  [FR] 1-(5-TERT-BUTYL-2-PHÉNYL-2H-PYRAZOL-3-YL)-3-[2-FLUORO-4-(1-MÉTHYL-2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-7-YLOXY)-PHÉNYL]-URÉE ET COMPOSÉS ASSOCIÉS, ET LEUR UTILISATION DANS DES TRAITEMENTS

  摘要：

  公开号：

  WO2011092469A8
• 作为产物：
  描述：

  4-(Boc-氨基)-3-氟苯酚 在 10% palladium on activated charcoal 吡啶 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 乙酸乙酯 、 mineral oil 为溶剂， 反应 30.75h， 生成 ethyl 4-(4-(tert-butoxycarbonyl)amino-3-fluorophenoxy)-2-aminopyridin-3-yl-carbamate
  参考文献：
  名称：

  [EN] 1-(5-TERT-BUTYL-2-PHENYL-2H-PYRAZOL-3-YL)-3-[2-FLUORO-4-(1-METHYL-2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-7-YLOXY)-PHENYL]-UREA AND RELATED COMPOUNDS AND THEIR USE IN THERAPY
  [FR] 1-(5-TERT-BUTYL-2-PHÉNYL-2H-PYRAZOL-3-YL)-3-[2-FLUORO-4-(1-MÉTHYL-2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-7-YLOXY)-PHÉNYL]-URÉE ET COMPOSÉS ASSOCIÉS, ET LEUR UTILISATION DANS DES TRAITEMENTS

  摘要：

  公开号：

  WO2011092469A8

文献信息

• 1-(5-TERT-BUTYL-2-PHENYL-2H-PYRAZOL-3-YL)-3-[2-FLUORO-4-(1-METHYL-2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-7-YLOXY)-PHENYL]-UREA AND RELATED COMPOUNDS AND THEIR USE IN THERAPY
  申请人：Springer Caroline

  公开号：US20120283288A1

  公开（公告）日：2012-11-08

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain compounds of the following formula (I) (for convenience, collectively referred to herein as “IP compounds”), which, inter alia, are useful in the treatment of cancer, e.g., cancer characterised by (e.g., driven by) mutant RAS (“mutant RAS cancer”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions in the treatment of cancer, e.g., mutant RAS cancer.

  本发明一般涉及治疗化合物领域，更具体地涉及以下式(I)的某些化合物（为方便起见，本文中统称为“IP化合物”），这些化合物可用于治疗癌症，例如由突变RAS（“突变RAS癌症”）特征化的癌症。本发明还涉及包含这种化合物的药物组合物，以及使用这种化合物和组合物治疗癌症，例如突变RAS癌症。
• 1-(5-TERT-BUTYL-2-PHENYL-2H-PYRAZOL-3-YL)-3-[2-FLUORO-4-(1-METHYL- 2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-7-YLOXY)-PHENYL]-UREA AND RELATED COMPOUNDS AND THEIR USE IN THERAPY
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US20140357663A1

  公开（公告）日：2014-12-04

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain compounds of the following formula (for convenience, collectively referred to herein as “IP compounds”), which, inter alia, are useful in the treatment of cancer, e.g., cancer characterised by (e.g., driven by) mutant RAS (“mutant RAS cancer”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions in the treatment of cancer, e.g., mutant RAS cancer.

  本发明通常涉及治疗化合物领域，更具体地涉及以下式子的某些化合物（为方便起见，在此统称为“IP化合物”），这些化合物等可用于治疗癌症，例如，由突变RAS（“突变RAS癌症”）特征化的癌症。本发明还涉及包含这种化合物的药物组合物以及在治疗癌症，例如突变RAS癌症中使用这种化合物和组合物的用途。
• Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring
  作者：Delphine Ménard、Ion Niculescu-Duvaz、Harmen P. Dijkstra、Dan Niculescu-Duvaz、Bart M. J. M. Suijkerbuijk、Alfonso Zambon、Arnaud Nourry、Esteban Roman、Lawrence Davies、Helen A. Manne、Frank Friedlos、Ruth Kirk、Steven Whittaker、Adrian Gill、Richard D. Taylor、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm900242c

  日期：2009.7.9

  BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have developed a series of small-molecule BRAF inhibitors based on a 1H-imidazo[4,5-b]pyridine-2(3H)-one scaffold (ring A) as the hinge binding moiety and a number Of Substituted phenyl rings C that interact with the allosteric binding site. The introduction of various groups on the central phenyl ring B combined with appropriate A- and C-ring modifications afford very potent compounds that inhibit (V600E)BRAF kinase activity in vitro and oncogqnic BRAF signaling in melanoma cells. Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC50 of 1 nM for purified (V600E)BRAF and nanomolar activity in cells.
• US8815896B2
  申请人：——

  公开号：US8815896B2

  公开（公告）日：2014-08-26
• US9120789B2
  申请人：——

  公开号：US9120789B2

  公开（公告）日：2015-09-01