6,7-dimethoxyquinoline-3-carboxylic acid | 5278-40-0

• 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: 6,7-dimethoxyquinoline-3-carboxylic acid
• 英文别名: carboxylic acid；6,7-Dimethoxy-3-quinolinecarboxylic acid
• CAS: 5278-40-0
• 化学式: C₁₂H₁₁NO₄
• 分子量: 233.224
• InChiKey: FIAMZJGNBUAXNB-UHFFFAOYSA-N

物化性质

• 熔点：
  140-141 °C
• 沸点：
  403.4±40.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxyquinoline-3-carboxylic acid 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 N-(3-carbonyloxy-(1-methyl-6,7-dimethoxyquinolinium))pyrolidine-2,5-dione triflate
  参考文献：
  名称：

  New developments in redox chemical delivery systems by means of 1,4-dihydroquinoline-based targetor: Application to galantamine delivery to the brain

  摘要：

  The therapeutic efficiency of palliative treatments of AD, mostly based on acetylcholinesterase (AChE) inhibitors, is marred by serious adverse effects due to peripheral activity of these AChE inhibitors. In the literature, a redox-based chemical delivery system (CDS) has been developed to enhance drugs distribution to the brain while reducing peripheral side effects. Herein, we disclose two new synthetic strategies for the preparation of 1,4-dihydroquinoline/quinolinium salt redox-based systems particularly well designed for brain delivery of drugs sensitive to alkylation reactions. These strategies have been applied in the present case to the AChE inhibitor galantamine with the aim of alleviating adverse effects observed with cholinergic AD treatment. The first strategy is based on an intramolecular alkylation reaction as key step, whilst the second strategy relies on a useful coupling between galantamine and quinolinium salt key intermediate. In the course of this work, polymer-supported reagents and a solid-phase synthesis approach revealed to be highly helpful to develop this redox-based galantamine CDS. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.022
• 作为产物：
  描述：

  6,7-dimethoxyquinoline-3-carbonitrile 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 20.0h， 以85%的产率得到6,7-dimethoxyquinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis, radiosynthesis and biological evaluation of 1,4-dihydroquinoline derivatives as new carriers for specific brain delivery

  摘要：

  尽管有许多关于使用1,4-二氢吡啶作为载体将生物活性化合物递送至大脑的报道，但这种化学递送系统（CDS）受到1,4-二氢吡啶衍生物对氧化和水合反应稳定性差的严重限制，从而限制了体内进一步研究。为了克服这些限制，我们在此首次报道了更稳定的环联式NADH模型在喹啉系列中的生物学评估，这些模型作为相关的神经活性药物载体候选物。制备了放射性标记的1,4-二氢喹啉[11C]1a以随后在 rats 中进行外周注射。注射的动物被牺牲并收集大脑。在 rat 大脑中测得的放射活性表明载体[11C]1a快速渗透至中枢神经系统（CNS）。对脑组织匀浆的高效液相色谱（HPLC）分析显示，[11C]1a氧化为相应的喹啉盐[11C]4a的过程在不到5分钟内完成。还报道了在 mice 中的体内评估，以说明这类1,4-二氢喹啉衍生物在CNS中运输神经活性药物的潜力。为此目的，将 γ-氨基丁酸（GABA）——因其难以穿越血脑屏障（BBB）而闻名——连接到这种1,4-二氢喹啉型载体上。在 mice 中腹腔注射1,4-二氢喹啉-GABA衍生物1b后，观察到运动活动（LMA）的显著改变，这可能是由于中枢GABA能活性的增强所致。这些令人鼓舞的结果为1b载体-GABA衍生物穿越BBB并在CNS中发挥药理作用的能力提供了有力证据。这项研究为设计新的氧化还原化学递送系统开辟了道路。

  DOI：

  10.1039/b909650g

文献信息

• Preparation of 1,4-Dihydroquinolines Bearing a Chiral Sulfoxide Group: New Highly Enantioselective Recyclable NADH Mimics
  作者：Vincent Levacher、Stéphane Gaillard、Cyril Papamicaël、Francis Marsais、Georges Dupas

  DOI：10.1055/s-2005-862350

  日期：——

  The stereoselective preparation of 1,4-dihydroquinolines possessing a chiral sulfoxide group at C-3 is reported. These novel biomimetic NADH models (R)-la,b have been shown to be highly enantioselective in the reduction of methyl benzoylformate, producing (R)-methyl mandelate in up to 95% ee. The corresponding quinolinium salts 4a,b have been recovered in good yields. The regenerated models la,b could

  报道了在 C-3 上具有手性亚砜基团的 1,4-二氢喹啉的立体选择性制备。这些新型仿生 NADH 模型 (R)-1a,b 已被证明在还原苯甲酰甲酸甲酯方面具有高度的对映选择性，可产生高达 95% ee 的 (R)-扁桃酸甲酯。相应的喹啉盐 4a、b 已以良好的收率回收。再生模型 1a,b 可以重复使用而不会显着降低对映选择性。
• New Efficient Conditions for the Reduction with NADH Models
  作者：J. L. Vasse、P. Charpentier、V. Levacher、G. Dupas、G. Quéguiner、J. Bourguignon

  DOI：10.1055/s-1998-1876

  日期：1998.10

  New conditions were used for the efficient reduction of various nitroalkenes and two prochiral ketones by using NADH mimics. The present procedure is very useful since it does not involve magnesium perchlorate which is replaced by magnesium bromide in THF. High conversions were observed. The new conditions were checked in asymmetric reductions.

  采用新的条件，通过使用NADH类物质有效还原了多种亚硝基烯烃和两个前手性酮。这一方法非常实用，因为它不涉及过氯酸镁，而是用溴化镁替代，溶剂为四氢呋喃。观察到了高转化率。新条件在不对称还原中得到了验证。
• Heterocyclic hydrazide derivatives of monocyclic beta-lactam antibiotics
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0420069A2

  公开（公告）日：1991-04-03

  Antibacterial activity has been found in compounds of the formula and pharmaceutically acceptable salts thereof, wherein: A is a bond or alkylene; Q completes a 5- or 6-membered saturated or aromatic heterocyclic ring optionally having an oxo substituent and and comprising up to two heteroatoms independently selected from N, NRs, S, O. Y is hydrogen, amino, hydroxy, carboxyl (provided that when Y is carboxyl the heterocyclic ring is not part of a quinoxaline or quinoline group), halogen, carboxamide, or nitrile; M⊕ is hydrogen or a cation; and the remaining symbols are as defined in the specification.

  式中的化合物及其药物可接受盐具有抗菌活性。 及其药学上可接受的盐，其中 A 是键或亚烷基； Q 完成一个 5 或 6 元饱和或芳香杂环，任选具有一个氧代基，并包含最多两个独立选自 N、NRs、S、O 的杂原子。 Y 是氢、氨基、羟基、羧基（条件是当 Y 是羧基时，杂环不是喹喔啉或喹啉基团的一部分）、卤素、羧酰胺或腈； M⊕ 是氢或阳离子；其余符号如说明书中所定义。
• SAR of novel benzothiazoles targeting an allosteric pocket of DENV and ZIKV NS2B/NS3 proteases
  作者：Hannah Maus、Fabian Barthels、Stefan Josef Hammerschmidt、Katja Kopp、Benedikt Millies、Andrea Gellert、Alessia Ruggieri、Tanja Schirmeister

  DOI：10.1016/j.bmc.2021.116392

  日期：2021.10
• Synthesis, electrophysiological properties and analysis of structural requirements of a novel class of antiarrhythmic agents with potassium and calcium channel blocking properties
  作者：Guy Nadler、Jean-François Faivre、Marie-Claire Forest、Brigitte Cheval、Michel Martin、Michel Souchet、Bernard Gout、Antoine Bril

  DOI：10.1016/s0968-0896(98)00166-7

  日期：1998.11

  Class III antiarrhythmic agents have been shown to prevent reentrant arrhythmias but also to be responsible for initiating arrhythmias characterised by afterdepolarizations and triggered activities. By combining potassium and calcium channel antagonistic actions, as with BRL-32872(1,2) (1), it might be possible to reduce the incidence of proarrhythmias albeit retaining antiarrhythmic efficacy. In the present study we synthesised and tested for their electrophysiological activity in guinea pig papillary muscle a wide panel of analogues of BRL-32872. Some qualitative relationships between compound structure and the inhibitory effect on the rapidly activating component of the delayed rectifier potassium current and/or the L-type calcium current will be presented. New derivatives depicting bell-shaped dose-response curves on action potential duration may therefore represent novel agents for improved antiarrhythmic therapy. (C) 1998 Elsevier Science Ltd. All rights reserved.