1H-Imidazo[4,5-c]quinoline, 1-methyl- | 99010-39-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1H-Imidazo[4,5-c]quinoline, 1-methyl-
• 英文别名: 1-methylimidazo[4,5-c]quinoline
• CAS: 99010-39-6
• 化学式: C₁₁H₉N₃
• 分子量: 183.213
• InChiKey: MBEOKCONJLQHKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1H-Imidazo[4,5-c]quinoline, 1-methyl- 在 platinum(IV) oxide 氢气 、 双氧水 、 乙酸酐 、 sodium hydride 作用下， 以 溶剂黄146 、 三氟乙酸 为溶剂， 25.0~80.0 ℃ 、413.69 kPa 条件下， 反应 135.5h， 生成 5-butyl-1-methyl-6,7,8,9-tetrahydro-1H-imidazo<4,5-c>quinolin-4(5H)-one
  参考文献：
  名称：

  New bronchodilators. 1. 1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones

  摘要：

  A series of novel xanthine-based tricyclic heterocycles in 1H-imidazo[4,5-c]quinolin-4(5H)-ones was designed, synthesized, and tested as potential active bronchodilators. Inhibition of the Schulz-Dale (SD) reaction-induced contraction in trachea and inhibition of antigen inhalation-induced bronchospasm in passively sensitized guinea pigs served as primary in vitro and in vivo assays, respectively. Simultaneous measurement of acute lethal toxicity (minimum lethal dose; MLD, po) in mice allowed determination of a safety margin. The bronchodilatory activity of these heterocycles was considerably varied with the nature of substituents at the 5-position. The most active substituents at the 2- and 5-positions and on the aromatic ring were found to be hydrogen, n-butyl, and hydrogen, respectively. There was a bulk tolerance for lipophilic substituents at the 1-position. 5-Butyl-substituted compounds appeared to be less toxic than theophylline on the basis of MLD data. Thus 5-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-4(5H)-one (10) (IC50 value of the SD assay = 0.25 muM, MLD > 300 mg/kg) was selected for further studies. Compound 10 (KF15570) reduced bronchoconstriction produced by antigen (Konzett-Rossler preparation in anesthetized guinea pigs, ED50 = 0.42 mg/kg, iv) more effectively than aminophylline (ethylenediamine salt of theophylline, ED50 = 7.8 mg/kg, iv) but had fewer side effects on the heart and CNS than theophylline. Compound 10 and its derivatives showed weak adenosine antagonism and phosphodiesterase (PDE) inhibition which could not account for their potent bronchodilation. Although their precise mechanism of action remains unclear, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

  DOI：

  10.1021/jm00100a009
• 作为产物：
  描述：

  4-(methylamino)-3-nitroquinoline 在 platinum on activated charcoal 氢气 、 magnesium sulfate 作用下， 以 乙酸乙酯 为溶剂， 生成 1H-Imidazo[4,5-c]quinoline, 1-methyl-
  参考文献：
  名称：

  Synthesis and Structure−Activity-Relationships of 1H-Imidazo[4,5-c]quinolines That Induce Interferon Production

  摘要：

  1H-Imidazo-[4,5-c]quinolines were prepared while investigating novel nucleoside analogues as potential antiviral agents. While these compounds showed no direct antiviral activity when tested in a number of cell culture systems, some demonstrated potent inhibition of virus lesion development in an intravaginal guinea pig herpes simplex virus-2 assay. We have determined that the in vivo antiviral activity can be attributed to the ability of these molecules to induce the production of cytokines, especially interferon (IFN), in this model. Subsequently, we found that the compounds also induce in vitro production of IFN in human peripheral blood mononuclear cells (hPBMCs). The in vitro results reported herein and the in vivo results reported previously led to the discovery of imiquimod, 26, which was developed as a topical agent and has been approved for the treatment of genital warts, actinic keratosis, and superficial basal cell carcinoma.

  DOI：

  10.1021/jm049211v

文献信息

• Novel Imidazo[4,5-c]Quinoline And Imidazo[4,5-c][1,5]Naphthyridine Derivatives As LRRK2 Inhibitors
  申请人：Pfizer Inc.

  公开号：US20170073343A1

  公开（公告）日：2017-03-16

  The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof wherein R 1 , R 1a , R 1b , R 2 , R 4 , R 5 , R 6 , X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.

  本发明提供了新颖的咪唑并[4,5-c]喹啉和咪唑并[4,5-c][1,5]萘啉衍生物的化合物(I)及其药学上可接受的盐，其中R1、R1a、R1b、R2、R4、R5、R6、X和Z如规范中所定义。该发明还涉及包含化合物(I)的药物组合物，以及利用这些化合物治疗与LRRK2相关的疾病，如神经退行性疾病包括帕金森病或阿尔茨海默病、癌症、克罗恩病或麻风病。
• Methods , composition and preparations for delivery of immune response modifiers
  申请人：Zarraga E. Isidro Angelo

  公开号：US20070166384A1

  公开（公告）日：2007-07-19

  A soluble IRM-polymer complex, preparations thereof, and methods of use, wherein the soluble IRM-polymer complex includes one or more IRM compounds attached (e.g., covalently attached) to a polymer (e.g., an alkylene oxide-containing polymer).

  一种可溶性IRM-聚合物复合物，其制备方法以及使用方法，其中可溶性IRM-聚合物复合物包括一个或多个IRM化合物与聚合物（例如，含有烷基氧的聚合物）连接（例如，共价连接）的情况。
• 2-substituted carbonylimidazo[4,5-c]quinolines
  申请人：Shionogi & Co., Ltd.

  公开号：US04940714A1

  公开（公告）日：1990-07-10

  2-Substituted carbonylimidazo[4,5-c]quinolines of formula: ##STR1## having a high affinity for benzodiazepin receptor and showing an excellent psychostimulating action orally at a dose of 0.1-500 mg are provided through several routes.

  提供了几种途径合成具有高亲和力的苯二氮平受体和在口服剂量为0.1-500毫克时显示出优异的精神刺激作用的式为##STR1##的2-取代羰基咪唑[4,5-c]喹啉。
• 2-Substituted carbonylimidazo[4,5-c]quinolines
  申请人：SHIONOGI & CO., LTD.

  公开号：EP0329073A2

  公开（公告）日：1989-08-23

  2-Substituted carbonylimidazo[4,5-c]quinolines of formula: having a high affinity for benzodiazepin receptor and showing an excellent psychostimulating action orally at a dose of 0.1 - 500 mg are provided through several routes.

  式中的 2-取代羰基咪唑并[4,5-c]喹啉： 通过几种途径提供了对苯并二氮杂卓受体具有高亲和力、口服剂量为 0.1-500 毫克时具有极佳精神刺激作用的 2-取代碳酰亚胺基咪唑并[4,5-c]喹啉类化合物。
• Compounds and compositions as inhibitors of MEK
  申请人：NOVARTIS AG

  公开号：US10011599B2

  公开（公告）日：2018-07-03

  The present invention relates to compounds of formula I: in which n, R1, R2, R3a, R4 and R5 are defined in the Summary of the Invention; capable of inhibiting the activity of MEK. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of hyperproliferative diseases like cancer.

  本发明涉及式 I 的化合物： 其中 n、R1、R2、R3a、R4 和 R5 在发明概述中定义；能够抑制 MEK 的活性。本发明进一步提供了制备本发明化合物的工艺、包含此类化合物的药物制剂以及使用此类化合物和组合物治疗癌症等过度增殖性疾病的方法。