5-butyl-1-methyl-1H-imidazo<4,5-c>quinolin-4(5H)-one | 133305-92-7

• 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: 5-butyl-1-methyl-1H-imidazo<4,5-c>quinolin-4(5H)-one
• 英文别名: 5-n-Butyl-1-methyl-1H,5H-imidazo[4,5-c]quinolin-4-one；4H-Imidazo(4,5-c)quinolin-4-one, 1,5-dihydro-5-butyl-1-methyl-；5-butyl-1-methylimidazo[4,5-c]quinolin-4-one
• CAS: 133305-92-7
• 化学式: C₁₅H₁₇N₃O
• 分子量: 255.319
• InChiKey: CVLGNWUGFVTZRC-UHFFFAOYSA-N

物化性质

• 沸点：
  504.2±32.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-butyl-1-methyl-1H-imidazo<4,5-c>quinolin-4(5H)-one 在 platinum(IV) oxide 氢气 作用下， 以 三氟乙酸 为溶剂， 反应 120.0h， 以72%的产率得到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：

  N-(2-bromophenyl)-N-butyl-1H-1-methylimidazole-4-carboxamide 在 四丁基氯化铵 、 lead(IV) tetraacetate 、 碳酸氢钠 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 24.0h， 以85%的产率得到5-butyl-1-methyl-1H-imidazo<4,5-c>quinolin-4(5H)-one
  参考文献：
  名称：

  咪唑并[4,5- c ^ ]喹啉-4（5 ħ） -酮通过自由基环化

  摘要：

  三丁基锡自由基诱导的N-（2-溴苯基）-N丁基-1 H -1-甲基咪唑-4-羧酰胺3的环化反应生成5-丁基-3-甲基-3 H-咪唑[4,5- c ]喹啉-4（5 ħ） -酮5通过[1,2] -酰基重排。

  DOI：

  10.1002/jhet.5570300334

文献信息

• Imidazoquinolone derivatives
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US04994468A1

  公开（公告）日：1991-02-19

  Novel imidazoquinolone derivative represented by the formula (I); ##STR1## wherein R.sup.1 represents hydrogen, alkyl, cycloalkyl, alkenyl aralkyl, aralkenyl or substituted or unsubstituted aryl; X represents nitrogen or ##STR2## where R.sup.2 is hydrogen, hydroxyl, alkyl, cycloalkyl, alkenyl, aralkyl, aralkenyl, substituted or unsubstituted aryl, thiol, halogen, substituted or unsubstituted aromatic heterocyclic group, or --(CH.sub.2).sub.m CO.sub.2 R.sup.6 where R.sup.6 is hydrogen or lower alkyl and m is an integer of 0 to 3; Y represents oxygen or sulfur; R.sup.3 represents alkyl, cycloalkyl, alkoxyalkly, alkenyl, aralkyl, aralkenyl, --(CH.sub.2).sub.n -- Het where Het is substituted or unsubstituted aromatic heterocyclic group and n is an integer of 1 to 3 or --(CH.sub.2).sub.n CO.sub.2 R.sup.6a where n has the same meaning as defined above and R.sup.6a has the same meaning as defined as to R.sup.6 ; each of R.sup.4 and R.sup.5 independently represents hydrogen, lower alkyl, trifluoromethyl, cycloalkyl, halogen, hydroxyl, lower alkoxyl, lower alkylthio, nitro, amino, lower alkylamino, lower alkanoylamino, aroylamino, lower alkanoyl or aroyl; and a pharmaceutically acceptable salt thereof. The Compound (I) and a pharmaceutically acceptable salt thereof show bronchodilatory and antiallergic activities, and are useful for treating respiratory disorders such as bronchial asthma.

  新型咪唑喹酮衍生物的化学式（I）所代表的是：其中R.sup.1代表氢、烷基、环烷基、烯基芳基、烯基芳基或取代或未取代芳基；X代表氮或##STR2##其中R.sup.2为氢、羟基、烷基、环烷基、烯基、芳基、硫醇、卤素、取代或未取代芳香杂环基，或--（CH.sub.2）.sub.m CO.sub.2 R.sup.6，其中R.sup.6为氢或较低烷基，m为0到3的整数；Y代表氧或硫；R.sup.3代表烷基、环烷基、烷氧基烷基、烯基、芳基、烯基芳基、--（CH.sub.2）.sub.n -- Het，其中Het为取代或未取代芳香杂环基，n为1到3的整数，或--（CH.sub.2）.sub.n CO.sub.2 R.sup.6a，其中n具有上述定义的相同含义，R.sup.6a具有与R.sup.6相同的定义；R.sup.4和R.sup.5中的每一个独立地代表氢、较低烷基、三氟甲基、环烷基、卤素、羟基、较低烷氧基、较低烷基硫基、硝基、氨基、较低烷基氨基、较低烷酰胺基、芳酰胺基、较低烷酰基或芳酰基；以及其药学上可接受的盐。化合物（I）及其药学上可接受的盐具有支气管扩张和抗过敏活性，并且可用于治疗支气管哮喘等呼吸系统疾病。
• Synthesis of 1H-imidazo[4,5-c]quinolin-4(5H)-one via palladium-catalyzed cyclization of N-(2-bromophenyl)-1H-imidazole-4-carboxamide
  作者：Takeshi Kuroda、Fumio Suzuki

  DOI：10.1016/0040-4039(91)80443-a

  日期：1991.11

  A new heterocycle, 5-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-4(5H)-one has been synthesized using palladium-catalyzed cyclization. A yield of the cyclization was optimized by changing base, additive and reaction temperature.
• US4994468A
  申请人：——

  公开号：US4994468A

  公开（公告）日：1991-02-19
• 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.
• Synthesis of imidazo[4,5-<i>c</i>]quinolin-4(5<i>H</i>)-one<i>via</i>radical cyclization
  作者：Fumio Suzuki、Takeshi Kuroda

  DOI：10.1002/jhet.5570300334

  日期：1993.5

  The tributyltin radical-induced cyclization of N-(2-bromophenyl)-Nbutyl-1H-1-methylimidazole-4-carbox-amide 3 gave 5-butyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one 5 via [1,2]-acyl rearrangement.

  三丁基锡自由基诱导的N-（2-溴苯基）-N丁基-1 H -1-甲基咪唑-4-羧酰胺3的环化反应生成5-丁基-3-甲基-3 H-咪唑[4,5- c ]喹啉-4（5 ħ） -酮5通过[1,2] -酰基重排。