7-((4-aminonaphthalen-1-yl)oxy)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one | 1160825-69-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 7-((4-aminonaphthalen-1-yl)oxy)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one
• 英文别名: 7-(4-aminonaphthalen-1-yloxy)-1-N-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one；7-(4-aminonaphthalen-1-yl-oxy)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one；7-(4-aminonaphthalen-1-yl-oxy)-1-N-methyl-1H-imidazo[4,5-b]pyridine-2(3H)-one；7-[(4-Amino-1-naphthalenyl)oxy]-1,3-dihydro-1-methyl-2h-imidazo[4,5-b]pyridin-2-one；7-(4-aminonaphthalen-1-yl)oxy-1-methyl-3H-imidazo[4,5-b]pyridin-2-one
• CAS: 1160825-69-3
• 化学式: C₁₇H₁₄N₄O₂
• 分子量: 306.324
• InChiKey: MVRMHHRINLOPNB-UHFFFAOYSA-N

物化性质

• 沸点：
  466.9±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-((4-aminonaphthalen-1-yl)oxy)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one 、 3-(三氟甲氧基)苯甲酰氯 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 以48%的产率得到N-[4-[(1-methyl-2-oxo-3H-imidazo[4,5-b]pyridin-7-yl)oxy]naphthalen-1-yl]-3-(trifluoromethoxy)benzamide
  参考文献：
  名称：

  Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring

  摘要：

  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.

  DOI：

  10.1021/jm900242c
• 作为产物：
  描述：

  N-[2-amino-4-[[4-[[(1,1-dimethylethoxy)carbonyl]amino]-1-naphthalenyl]oxy]-3-pyridinyl]carbamic acid ethyl ester 在 sodium ethanolate 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 mineral oil 为溶剂， 反应 13.42h， 生成 7-((4-aminonaphthalen-1-yl)oxy)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one
  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

• RESPIRATORY FORMULATIONS AND COMPOUNDS FOR USE THEREIN
  申请人：Murray Peter John

  公开号：US20130156826A1

  公开（公告）日：2013-06-20

  The present invention relates to respiratory formulations comprising a compound of formula (I): and use of said compounds and compositions in treatment, for example in the treatment of an inflammatory disease or a respiratory disorder, in particular an inflammatory mediated and/or virally mediated respiratory disorder such as asthma and COPD or the treatment or prevention of viral infection, for example infection by influenza virus, rhinovirus or RSV. The invention also extends to certain novel compounds of formula (I).

  本发明涉及含有化合物的呼吸配方(I)：以及在治疗中使用这些化合物和组合物，例如在治疗炎症性疾病或呼吸道疾病中的应用，特别是在治疗由炎症介导和/或病毒介导的呼吸道疾病，如哮喘和慢性阻塞性肺病，或治疗或预防病毒感染，例如由流感病毒、鼻病毒或RSV感染。该发明还涉及某些新型化合物(I)。
• Development of Novel, Highly Potent Inhibitors of V-RAF Murine Sarcoma Viral Oncogene Homologue B1 (BRAF): Increasing Cellular Potency through Optimization of a Distal Heteroaromatic Group
  作者：Bart M. J. M. Suijkerbuijk、Ion Niculescu-Duvaz、Catherine Gaulon、Harmen P. Dijkstra、Dan Niculescu-Duvaz、Delphine Ménard、Alfonso Zambon、Arnaud Nourry、Lawrence Davies、Helen A. Manne、Frank Friedlos、Lesley M. Ogilvie、Douglas Hedley、Filipa Lopes、Natasha P. U. Preece、Javier Moreno-Farre、Florence I. Raynaud、Ruth Kirk、Steven Whittaker、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm900607f

  日期：2010.4.8

  We describe the design, synthesis, and optimization of a series of new inhibitors of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF), a kinase whose mutant form (V600E) is implicated in several types of cancer, with a particularly high frequency in melanoma. Our previously described inhibitors with a tripartite A−B−C system (where A is a hinge binding pyrido[4,5-b]imidazolone system, B is an

  我们描述了一系列新型V-RAF鼠肉瘤病毒癌基因同源物B1（BRAF）抑制剂的设计，合成和优化，该激酶的突变体形式（V600E）与几种类型的癌症有关，发生频率特别高在黑色素瘤中。我们先前所述的具有三方A-B-C系统的抑制剂（其中A是铰链结合吡啶并[4,5- b ]咪唑啉酮系统，B是芳基间隔基团，C是杂芳族基团）对纯化的V600E有效体外进行BRAF，但在伴随的细胞测定中效力较弱。本文评估将不同的芳族杂环取代为基于苯基的C环，作为提高这些抑制剂细胞效价的潜在手段。取代的吡唑，尤其是3-叔丁基-丁基-1-芳基-1 H-吡唑类可增加细胞效能，而对分离的V600E BRAF的效能无不利影响。因此，已经合成了以低纳摩尔浓度抑制V600E BRAF，其在细胞中的下游信号传导的化合物（如通过细胞外调节激酶（ERK）磷酸化的减少来测量）以及突变型BRAF依赖性细胞的增殖。伴随的好处是良好的口服生物利用度和体内高血浆浓度。
• 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。
• Respiratory formulations and compounds for use therein
  申请人：Respivert, Ltd.

  公开号：US10358445B2

  公开（公告）日：2019-07-23

  The present invention relates to respiratory formulations comprising a compound of formula (I): and use of said compounds and compositions in treatment, for example in the treatment of an inflammatory disease or a respiratory disorder, in particular an inflammatory mediated and/or virally mediated respiratory disorder such as asthma and COPD or the treatment or prevention of viral infection, for example infection by influenza virus, rhinovirus or RSV. The invention also extends to certain novel compounds of formula (I).

  本发明涉及包含式（I）化合物的呼吸制剂： 以及所述化合物和组合物在治疗中的应用，例如在治疗炎症性疾病或呼吸系统疾病，特别是炎症介导和/或病毒介导的呼吸系统疾病，如哮喘和慢性阻塞性肺病，或治疗或预防病毒感染，例如流感病毒、鼻病毒或 RSV 感染中的应用。本发明还涉及某些新型的式 (I) 化合物。