1-benzyl-1H-imidazo[4,5-c]quinoline | 99023-72-0

• 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: 1-benzyl-1H-imidazo[4,5-c]quinoline
• 英文别名: 1-Benzylimidazo[4,5-c]quinoline
• CAS: 99023-72-0
• 化学式: C₁₇H₁₃N₃
• 分子量: 259.31
• InChiKey: CPEONTQGAAFNBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 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：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-1H-imidazo[4,5-c]quinoline 在 双氧水 、 乙酸酐 、 sodium hydride 作用下， 以 溶剂黄146 为溶剂， 反应 15.5h， 生成 1-Benzyl-5-n-butyl-1H,5H-imidazo[4,5-c]quinolin-4-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：

  3-硝基-4-羟基喹啉 在 platinum on activated charcoal 氯化亚砜 、 氢气 、 magnesium sulfate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 1-benzyl-1H-imidazo[4,5-c]quinoline
  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

• 1H-imidazo[4,5-c]quinolines and their use as bronchodilating agents
  申请人：Riker Laboratories, Inc.

  公开号：US04698348A1

  公开（公告）日：1987-10-06

  1H-imidazo[4,5-c]quinoline which are bronchodilators. Pharmacological methods of using the compounds as bronchodilators, pharmaceutical compositions containing the compounds, and synthetic intermediate for preparing the compounds are also described.

  1H-咪唑并[4,5-c]喹啉是支气管扩张剂。描述了使用这些化合物作为支气管扩张剂的药理学方法，含有这些化合物的药物组合物，以及用于制备这些化合物的合成中间体。
• 1H-Imidazo[4,5-c]quinolin-4-amines and antiviral use
  申请人：Riker Laboratories, Inc.

  公开号：US04689338A1

  公开（公告）日：1987-08-25

  1H-Imidazo[4,5-c]quinolin-4-amines which are antivirals. Pharmacological methods of using such compounds and pharmaceutical compositions containing such compounds are also described.

  1H-咪唑并[4,5-c]喹啉-4-胺是抗病毒药物。还描述了使用这些化合物的药理学方法以及含有这些化合物的药物组合物。
• New Bronchodilators. II. 3H-Imidazo(4,5-c)quinolin-4(5H)-ones.
  作者：Fumio SUZUKI、Takeshi KURODA、Hiroaki HAYASHI、Yoshisuke NAKASATO、Haruhiko MANABE、Kenji OHMORI、Shigeto KITAMURA

  DOI：10.1248/cpb.40.3245

  日期：——

  A series of novel 3-substituted imidazo[4, 5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4, 5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen-induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5-position were more tolerant of the activity than those at the 3-position. 5-Ethyl-3-methyl-3H-imidazo[4, 5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo.

  一系列新型3-取代咪唑并[4,5-c]喹啉-4(5H)-酮（2a-w）是通过咪唑并[4,5-c]喹啉-4(5H)-酮（6）与几种电化合物的反应在碱性条件下制备的。这些化合物的支气管扩张活性是根据它们对豚鼠气管（体外）抗原诱导收缩（舒尔茨-戴尔反应）和被动致敏豚鼠（体内）抗原吸入诱导支气管痉挛的保护作用来评估的。虽然体外和体内活性之间的相关性尚不清楚，但3位上的甲基和乙基等短烷基链对于有效活性非常重要，特别是在体内。5位上的取代基比
• 1H-Imidazo[4,5-c]quinolines and 1H-imidazo[4,5-c]quinolin-4-amines
  申请人：RIKER LABORATORIES, INC.

  公开号：EP0145340B1

  公开（公告）日：1990-01-24
• Quinoline intermediates for the synthesis of 1H-imidazo[4,5-c]quinolines and 1H-imidazo[4,5-c]quinolin-4-amimes
  申请人：RIKER LABORATORIES, INC.

  公开号：EP0310950B1

  公开（公告）日：1993-01-13