1-benzyl-4-hydroxy-1H-imidazo<4,5-c>quinoline | 134049-86-8

• 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-4-hydroxy-1H-imidazo<4,5-c>quinoline
• 英文别名: 1-benzyl-5H-imidazo[4,5-c]quinolin-4-one
• CAS: 134049-86-8
• 化学式: C₁₇H₁₃N₃O
• 分子量: 275.31
• InChiKey: CZVWDAXJDWKHQM-UHFFFAOYSA-N

物化性质

• 沸点：
  446.6±14.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 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：
  46.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-4-hydroxy-1H-imidazo<4,5-c>quinoline 在 palladium on activated charcoal 氢气 、 sodium hydride 、 溶剂黄146 作用下， 反应 7.5h， 生成 5-Isobutyl-3-isopropyl-3,5-dihydro-imidazo[4,5-c]quinolin-4-one
  参考文献：
  名称：

  New Bronchodilators. II. 3H-Imidazo(4,5-c)quinolin-4(5H)-ones.

  摘要：

  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

  DOI：

  10.1248/cpb.40.3245
• 作为产物：
  描述：

  1-benzyl-1H-imidazo[4,5-c]quinoline 在 双氧水 、 sodium methylate 、 乙酸酐 作用下， 以 溶剂黄146 为溶剂， 反应 13.0h， 生成 1-benzyl-4-hydroxy-1H-imidazo<4,5-c>quinoline
  参考文献：
  名称：

  New Bronchodilators. II. 3H-Imidazo(4,5-c)quinolin-4(5H)-ones.

  摘要：

  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

  DOI：

  10.1248/cpb.40.3245

文献信息

• Imidazoquinolone derivates
  申请人：KYOWA HAKKO KOGYO CO., LTD.

  公开号：EP0411394A1

  公开（公告）日：1991-02-06

  Novel imidazoquinolone derivative represented by formula (I); wherein R¹ represents lower alkyl or -(CH₂)mCO-R³ where R³ represents hydrogen, lower alkyl, hydroxy or lower alkoxy; and m is an integer of 1 to 3; R² represents lower alkyl; or a pharmaceutically acceptable salt thereof.

  由式 (I) 代表的新型咪唑喹啉酮衍生物； 其中 R¹ 代表低级烷基或 -(CH₂)mCO-R³ 其中 R³ 代表氢、低级烷基、羟基或低级烷氧基；且 m 为 1 至 3 的整数； R² 代表低级烷基； 或其药学上可接受的盐。
• New bronchodilators. 1. 1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones
  作者：Fumio Suzuki、Takeshi Kuroda、Yoshisuke Nakasato、Haruhiko Manabe、Kenji Ohmori、Shigeto Kitamura、Shunji Ichikawa、Tetsuji Ohno

  DOI：10.1021/jm00100a009

  日期：1992.10

  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.
• US5010084A
  申请人：——

  公开号：US5010084A

  公开（公告）日：1991-04-23
• 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