((4-fluoro-3-nitrobenzyl)oxy)triisopropylsilane | 1366097-28-0

• 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: ((4-fluoro-3-nitrobenzyl)oxy)triisopropylsilane
• 英文别名: (4-Fluoro-3-nitrophenyl)methoxy-tri(propan-2-yl)silane
• CAS: 1366097-28-0
• 化学式: C₁₆H₂₆FNO₃Si
• 分子量: 327.471
• InChiKey: NPAJVRCFZLFENK-UHFFFAOYSA-N

物化性质

• 沸点：
  372.0±27.0 °C(Predicted)
• 密度：
  1.044±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.43
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ((4-fluoro-3-nitrobenzyl)oxy)triisopropylsilane 在 2,6-二甲基吡啶 、 盐酸 、 palladium on activated charcoal 、 四丁基氟化铵 、 氢气 、 戴斯-马丁氧化剂 、 三乙胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.5h， 生成 (E)-1⁵-((4-methylpiperazin-1-yl)methyl)-1²,1³-dihydro-1¹H-2,6-diaza-1(2,1)-benzo[d]imidazola-4(2,6)-pyridinacycloundecaphane-3,5-dione
  参考文献：
  名称：

  [EN] MACROCYCLIC TAK1 INHIBITORS
  [FR] INHIBITEURS MACROCYCLIQUES DE TAK1

  摘要：

  The invention provides a compound according to formula (I) or a tautomer thereof, wherein R1, R2, R3, W1, W2, W3, A, X and Y are as defined in the specification. The compounds are potent inhibitors of the serine/threonine kinase, TAK1. The present invention further provides: a pharmaceutical composition comprising a compound of formula (I) and at least one pharmaceutically acceptable excipient; a compound of formula (I) for use as a medicament (for example for the treatment or prophylaxis of a condition selected from cancer, inflammatory diseases, autoinflammatory diseases and autoimmune diseases); and a method of treating or preventing a disease or disorder comprising administering a pharmaceutically effective amount of a compound of formula (I) to a subject in need thereof.

  公开号：

  WO2023275199A1
• 作为产物：
  描述：

  4-氟-3-硝基苄醇 、 三异丙基硅基三氟甲磺酸酯 在 2,6-二甲基吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 ((4-fluoro-3-nitrobenzyl)oxy)triisopropylsilane
  参考文献：
  名称：

  [EN] NOVEL UREA DERIVATIVES AS TEC KINASE INHIBITORS AND USES THEREOF
  [FR] NOUVEAUX DÉRIVÉS D'URÉE EN TANT QU'INHIBITEURS DE KINASE TEC ET LEURS UTILISATIONS

  摘要：

  提供的是式（I）的尿素化合物，作为Tec激酶抑制剂，特别是ITK（白细胞介素-2诱导酪氨酸激酶）抑制剂。本文还提供了制备所述化合物的方法、用于合成的中间体、药物组合物以及治疗或预防由ITK介导的疾病、状况和/或紊乱的方法。

  公开号：

  WO2013024427A1

文献信息

• [EN] SUBSTITUTED BENZIMIDAZOLE COMPOUNDS<br/>[FR] COMPOSES BENZIMIDAZOLE SUBSTITUES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2004014905A1

  公开（公告）日：2004-02-19

  Disclosed are substituted benzimidazole compounds of formula (I) wherein R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and the pharmaceutical compositions comprising these compounds.

  揭示了一种化学式（I）中的取代苯并咪唑化合物，其中R1、R2、R3、R4和Xa在此处定义。该发明的化合物抑制Itk激酶，因此可用于治疗涉及炎症、免疫紊乱和过敏性疾病的疾病和病理状况。还揭示了制备这些化合物的方法以及包含这些化合物的药物组合物。
• 5-Aminomethylbenzimidazoles as potent ITK antagonists
  作者：Doris Riether、Renée Zindell、Jennifer A. Kowalski、Brian N. Cook、Jörg Bentzien、Stéphane De Lombaert、David Thomson、Stanley Z. Kugler、Donna Skow、Leslie S. Martin、Ernest L. Raymond、Hnin Hnin Khine、Kathy O’Shea、Joseph R. Woska、Deborah Jeanfavre、Rosemarie Sellati、Kerry L.M. Ralph、Jennifer Ahlberg、Gabriel Labissiere、Mohammed A. Kashem、Steven S. Pullen、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2009.02.012

  日期：2009.3

  Benzamide 1 demonstrated good potency as a selective ITK inhibitor, however the amide moiety was found to be hydrolytically labile in vivo, resulting in low oral exposure and the generation of mutagenic aromatic amine metabolites. Replacing the benzamide with a benzylamine linker not only addressed the toxicity issue, but also improved the cellular and functional potency as well as the drug-like properties. SAR studies around the benzylamines and the identification of 10n and 10o as excellent tools for proof-of-concept studies are described. (C) 2009 Elsevier Ltd. All rights reserved.
• 5-Aminomethyl-1H-benzimidazoles as orally active inhibitors of inducible T-cell kinase (Itk)
  作者：Michael P. Winters、Darius J. Robinson、Hnin Hnin Khine、Steven S. Pullen、Joseph R. Woska、Ernest L. Raymond、Rosemarie Sellati、Charles L. Cywin、Roger J. Snow、Mohammed A. Kashem、John P. Wolak、Josephine King、Paul V. Kaplita、Lisa H. Liu、Thomas M. Farrell、Renee DesJarlais、Gregory P. Roth、Hidenori Takahashi、Kevin J. Moriarty

  DOI：10.1016/j.bmcl.2008.09.016

  日期：2008.10

  A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were prepared. Structure activity relationships, selectivity and cell activity are reported for this series. Compound 2, a potent and selective antagonist of Itk, inhibited anti-CD3 antibody induced IL-2 production in vivo in mice. (c) 2008 Elsevier Ltd. All rights reserved.
• [EN] NOVEL UREA DERIVATIVES AS TEC KINASE INHIBITORS AND USES THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS D'URÉE EN TANT QU'INHIBITEURS DE KINASE TEC ET LEURS UTILISATIONS
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2013024427A1

  公开（公告）日：2013-02-21

  Provided are urea compounds of formula (I) as Tec kinase inhibitors, in particular ITK (interleukin-2 inducible tyrosine kinase) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders mediated by ITK.

  提供的是式（I）的尿素化合物，作为Tec激酶抑制剂，特别是ITK（白细胞介素-2诱导酪氨酸激酶）抑制剂。本文还提供了制备所述化合物的方法、用于合成的中间体、药物组合物以及治疗或预防由ITK介导的疾病、状况和/或紊乱的方法。
• [EN] MACROCYCLIC TAK1 INHIBITORS<br/>[FR] INHIBITEURS MACROCYCLIQUES DE TAK1
  申请人：[en]AQILION AB

  公开号：WO2023275199A1

  公开（公告）日：2023-01-05

  The invention provides a compound according to formula (I) or a tautomer thereof, wherein R1, R2, R3, W1, W2, W3, A, X and Y are as defined in the specification. The compounds are potent inhibitors of the serine/threonine kinase, TAK1. The present invention further provides: a pharmaceutical composition comprising a compound of formula (I) and at least one pharmaceutically acceptable excipient; a compound of formula (I) for use as a medicament (for example for the treatment or prophylaxis of a condition selected from cancer, inflammatory diseases, autoinflammatory diseases and autoimmune diseases); and a method of treating or preventing a disease or disorder comprising administering a pharmaceutically effective amount of a compound of formula (I) to a subject in need thereof.