butylisatoic anhydride | 16512-56-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: butylisatoic anhydride
• 英文别名: 1-butylisatoic anhydride；1-Butyl-1H-<3,1>benzoxazine-2,4-dione；N-Butylisatoinsaeureanhydrid；N-butylisatoic acid anhydride；1-butyl-1H-benzo[d][1,3]oxazine-2,4-dione；1-butyl-2H-3,1-benzoxazine-2,4(1H)-dione；N-(n-butyl)isatoic anhydride；N-butylisatoic anhydride；2H-3,1-Benzoxazine-2,4(1H)-dione, 1-butyl-；1-butyl-3,1-benzoxazine-2,4-dione
• CAS: 16512-56-4
• 化学式: C₁₂H₁₃NO₃
• mdl: MFCD06490511
• 分子量: 219.24
• InChiKey: GNXNHIFZVKBXAK-UHFFFAOYSA-N

物化性质

• 熔点：
  74 °C
• 沸点：
  337.1±25.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)
• 溶解度：
  二氯甲烷；

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  butylisatoic anhydride 在 platinum(IV) oxide 、 palladium on activated charcoal 氢气 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 三氟乙酸 为溶剂， 120.0 ℃ 、413.69 kPa 条件下， 反应 143.0h， 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：

  正溴丁烷 、 靛红酸酐 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 22.0h， 生成 butylisatoic anhydride
  参考文献：
  名称：

  制备4-羟基喹啉酮酯的实用方法

  摘要：

  4-羟基喹啉酮酯是许多药物的常见基序。存在几种制备这些化合物的方法，通常涉及氢化钠的使用，这引起了显着的安全性问题并且限制了它们在大规模合成中的应用。在此说明中，描述了一种实用，安全且通用的方法，该方法采用了二异丙基乙胺和叔丁醇钠的组合。这允许以良好的产率合成4-羟基喹啉酮酯和酰胺。

  DOI：

  10.1021/jo071200x

文献信息

• Palladium-Catalyzed Cyclization Reaction of <i>o</i>-Iodoanilines, CO₂, and CO: Access to Isatoic Anhydrides
  作者：Wen-Zhen Zhang、Ning Zhang、Yu-Qian Sun、Yu-Wei Ding、Xiao-Bing Lu

  DOI：10.1021/acscatal.7b03000

  日期：2017.12.1

  oxidants. Herein we report a highly selective palladium-catalyzed cyclization reaction for the efficient synthesis of isatoic anhydrides from readily available o-iodoanilines, CO2, and CO. The reaction proceeds under mild conditions and is redox-neutral. Both CO2 and CO are indispensable C1 building blocks for this catalytic reaction.

  通常使用高毒性的光气或化学计量的氧化剂来制备一类酸酐，一类有价值的合成中间体和RNA结构探测试剂。本文中，我们报道了一种高度选择性的钯催化环化反应，用于从容易获得的邻碘代苯胺，CO 2和CO有效合成isatoic酸酐。该反应在温和的条件下进行，并且是氧化还原中性的。对于该催化反应，CO 2和CO都是不可或缺的C1结构单元。
• Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT
  作者：Rachel L. Clark、Carol J. Clements、Michael P. Barrett、Simon P. Mackay、Rajendra P. Rathnam、George Owusu-Dapaah、John Spencer、Judith K. Huggan

  DOI：10.1016/j.bmc.2012.08.049

  日期：2012.10

  A library of 1,4-benzodiazepines has been synthesised and evaluated for activity against Trypanosoma brucei, a causative parasite of Human African Trypanosomiasis (HAT). The most potent of these derivatives has an MIC value of 0.97 μM. Herein we report the design, synthesis and biological evaluation of the abovementioned compounds.

  合成了一个1,4-苯并二氮杂卓的文库，并评估了其对布鲁氏锥虫（人类非洲锥虫病（HAT）的致病性寄生虫）的活性。这些衍生物中最有效的MIC值为0.97μM。本文中我们报告了上述化合物的设计，合成和生物学评估。
• Pharmaceutical preparation and use of
  申请人：Sandoz, Inc.

  公开号：US04190659A1

  公开（公告）日：1980-02-26

  Disclosed are compounds which are 4-hydroxy-2-quinolinone-3-carboxylic acid esters, e.g., 1-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester, useful as anti-allergic agents and intermediates for 1-alkyl-4-alkoxy-quinolin-2(1H)-ones, and prepared by reacting an isatoic anhydride with an alkali metal salt of a malonic ester.

  公开了化合物，这些化合物是4-羟基-2-喹啉酮-3-羧酸酯，例如，1-甲基-4-羟基-2-喹啉酮-3-羧酸乙酯，可用作抗过敏剂和1-烷基-4-烷氧基-喹啉-2(1H)-酮的中间体，并通过将异烟酰酐与丙二酸酯的碱金属盐反应制备而成。
• One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous Biscyclization Reaction
  作者：Zi-Xuan Wang、Jia-Chen Xiang、Miao Wang、Jin-Tian Ma、Yan-Dong Wu、An-Xin Wu

  DOI：10.1021/acs.orglett.8b02667

  日期：2018.10.19

  The one-pot total synthesis of evodiamine and its analogues is achieved using a three-component reaction. Through continuous biscyclization, various readily available substrates with good functional group tolerance were easily incorporated into biologically active quinazolinocarboline backbones. The use of triethoxymethane as a cosolvent was crucial for this quick and straightforward transformation

  使用三组分反应可实现一锅法合成乙二胺及其类似物。通过连续的双环化，容易将具有良好官能团耐受性的各种容易获得的底物掺入具有生物活性的喹唑啉代咔啉主链中。三乙氧基甲烷作为助溶剂的使用对于这种快速而直接的转化至关重要。
• 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。