6-氟-1,2,3,4-四氢喹喔啉-2-酮 | 148010-65-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 6-氟-1,2,3,4-四氢喹喔啉-2-酮
• 英文名称: 6-fluoro-3,4-dihydroquinoxalin-2(1H)-one
• 英文别名: 6-fluoro-3,4-dihydro-1H-quinoxalin-2-one
• CAS: 148010-65-5
• 化学式: C₈H₇FN₂O
• 分子量: 166.155
• InChiKey: MAUOZEMZZULUTF-UHFFFAOYSA-N

物化性质

• 熔点：
  165-169 °C
• 沸点：
  347.9±42.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-氟-1,2,3,4-四氢喹喔啉-2-酮 在 potassium tert-butylate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 叔丁醇 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.5h， 生成 tert-butyl 5-[(2R,6S)-2,6-dimethylpiperazine-1-carbonyl]-7-fluoro-4H-imidazo[1,5-a]quinoxaline-3-carboxylate
  参考文献：
  名称：

  Piperazine Imidazo[1,5-a]quinoxaline Ureas as High-Affinity GABA_A Ligands of Dual Functionality

  摘要：

  A series of imidazo[1,5-alpha]quinoxaline piperazine ureas appended with a tert-butyl ester side chain at the 3-position was developed. Analogues within this series have high affinity for the gamma-aminobutyric acid A (GABA(A))/benzodiazepine receptor complex with efficacies ranging from inverse agonists to full agonists. Many analogues were found to be partial agonists as indicated by [S-35]TBPS and Cl- current ratios. Uniquely, a number of these analogues were found to have a bell-shaped dose-response profile in the alpha(1)beta(2)gamma(2) subtype as determined by whole cell patch-clamp technique, where in vitro efficacy was found to decrease with increasing drug concentration. Many of the compounds from this series were effective in antagonizing metrazole-induced seizures, consistent with anticonvulsant and possibly anxiolytic activity. Additionally, several analogues were also effective in lowering cGMP levels (to control values) after applied stress, also consistent with anxiolytic-like properties. The most effective compounds in these screens were also active in animal models of anxiety such as the Vogel and Geller assays. The use of the piperazine substituent allowed for excellent drug levels and a long duration of action in the central nervous system for many of the quinoxalines, as determined by ex vivo assay. Pharmacokinetic analysis of several compounds indicated excellent oral bioavailability and a reasonable half-life in rats. From this series emerged two partial agonists (55, 91) which had good activity in anxiolytic models, acceptable pharmacokinetics, and minimal benzodiazepine-type side effects.

  DOI：

  10.1021/jm9801307
• 作为产物：
  描述：

  3-chloro-6-fluoroquinoxalin-2(1H)-one-4-oxide 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以83%的产率得到6-氟-1,2,3,4-四氢喹喔啉-2-酮
  参考文献：
  名称：

  通过选择性修饰 3-Chloro-6-fluoroquinoxalin-2(1H)-one 4-Oxide 高效合成喹喔啉衍生物

  摘要：

  易于获得的多官能化 3-chloro-6-fluoroquinoxalin-2(1H)-one 4-oxide，源自 1,1,2-trichloro-2-nitroethene 与 4-fluoroaniline 的高效一步环化反应，是在氯硝酮和酰胺单元上进行选择性修饰，产生了 30 多种新的喹喔啉衍生物，它们具有独特的取代模式，产率很高。此外，通用起始化合物的电子性质是通过密度泛函理论计算的，这对其独特的反应性给出了合理的解释。已经研究了所有迄今为止未知的化合物的抗疟活性。

  DOI：

  10.1002/ejoc.201201569

文献信息

• Photocatalytic Giese Addition of 1,4-Dihydroquinoxalin-2-ones to Electron-Poor Alkenes Using Visible Light
  作者：Jaume Rostoll-Berenguer、Gonzalo Blay、José R. Pedro、Carlos Vila

  DOI：10.1021/acs.orglett.0c02953

  日期：2020.10.16

  The optimized reaction conditions provide a good yield for the radical conjugate addition products (44 examples) with a wide range of structurally different Michael acceptors. A gram scale reaction using sunlight irradiation is also described. Furthermore, several transformations were carried out with the Giese addition products.

  使用Ru（bpy）3 Cl 2作为光催化剂和（PhO）2 PO 2 H作为添加剂，实现了1,4-二氢喹喔啉-2-酮与Michael受体的可见光光氧化还原催化偶联。优化的反应条件为具有广泛结构上不同的迈克尔受体的自由基共轭加成产物（44个实例）提供了良好的收率。还描述了使用阳光照射的克级反应。此外，使用Giese添加产品进行了几次转化。
• Antagonist, Partial Agonist, and Full Agonist Imidazo[1,5-a]quinoxaline Amides and Carbamates Acting through the GABAA/Benzodiazepine Receptor
  作者：Ruth E. TenBrink、Wha B. Im、Vimala H. Sethy、Andrew H. Tang、Don B. Carter

  DOI：10.1021/jm00032a008

  日期：1994.3

  carbamates, represent a new series of compounds which bind with high affinity to the GABAA/benzodiazepine receptor. These compounds exhibit a wide range of intrinsic efficacies as measured by [35S]TBPS binding ratios. The synthesis of 1a begins with the addition of DL-glutamic acid to 1-fluoro-2-nitrobenzene, followed by reduction of the nitro group and subsequent ring closure to form 3-(carbethoxymethyl)-1

  （4RS）-1-（5-环丙基-1,2-，4-恶二唑-3-基）-12,12a-二羟基咪唑并[1,5-a]吡咯并[2,1-c]喹喔啉-10（11H） ）-一（1a），5-苯甲酰基-3-（5-环丙基-1,2,4-恶二唑-3-基）-4,5-二氢咪唑并[1,5-a]喹喔啉（13b）和叔叔（4S）-12,12a-二氢咪唑并[1,5-a]吡咯并[2,1-c]喹喔啉-1-羧酸（1e）以及其他咪唑并[1,5-a]喹喔啉酰胺和氨基甲酸酯代表了一系列与GABAA /苯并二氮杂receptor受体具有高亲和力的化合物。通过[35S] TBPS结合比测量，这些化合物具有广泛的内在功效。1a的合成开始于将DL-谷氨酸添加到1-氟-2-硝基苯中，然后还原硝基并随后闭环形成3-（羧乙氧基甲基）-1,2,3,4-四氢喹喔啉-2-one，然后进行第二个环闭合，得到（4RS）-1，以5-二氧-1,2,3,4,5,6-六氢吡咯并[1
• Imidazo[1,5-A]quinoxalines
  申请人：The Upjohn Company

  公开号：US05541324A1

  公开（公告）日：1996-07-30

  An invention relating to Imidazo[1,5-a]quinoxalines (I) ##STR1## which do not contain an endocyclic carbonyl group and which are useful as anxiolytic and sedative/hypnotic agents.

  一种涉及咪唑并[1,5-a]喹喔啉(I)的发明，不含内环羰基，并且可用作抗焦虑和镇静/催眠剂。
• Fluorine-Containing 6,7-Dialkoxybiaryl-Based Inhibitors for Phosphodiesterase 10 A: Synthesis and in vitro Evaluation of Inhibitory Potency, Selectivity, and Metabolism
  作者：Gregor Schwan、Ghadir Barbar Asskar、Norbert Höfgen、Lenka Kubicova、Uta Funke、Ute Egerland、Michael Zahn、Karen Nieber、Matthias Scheunemann、Norbert Sträter、Peter Brust、Detlef Briel

  DOI：10.1002/cmdc.201300522

  日期：2014.7

  Based on the potent phosphodiesterase 10 A (PDE10A) inhibitor PQ‐10, we synthesized 32 derivatives to determine relationships between their molecular structure and binding properties. Their roles as potential positron emission tomography (PET) ligands were evaluated, as well as their inhibitory potency toward PDE10A and other PDEs, and their metabolic stability was determined in vitro. According to our

  基于有效的磷酸二酯酶10 A（PDE10A）抑制剂PQ-10，我们合成了32种衍生物，以确定其分子结构与结合特性之间的关系。评估了它们作为潜在的正电子发射断层扫描（PET）配体的作用，以及它们对PDE10A和其他PDE的抑制能力，并在体外确定了它们的代谢稳定性。根据我们的发现，喹唑啉部分2位的卤代烷基取代基和/或6位或7位的卤代烷氧基取代基不仅影响化合物的亲和力，而且还影响其对PDE10A的选择性。由于在喹唑啉环的6位上用甲氧基取代了单氟乙氧基或二氟乙氧基，PDE10A相对于PDE3A的选择性增加了。通过6获得相同的结果 喹喔啉部分上的7-二氟取代。最后，氟化物（R）-7-（氟甲氧基）-6-甲氧基-4-（3-（喹喔啉-2-基氧基）吡咯烷-1-基）喹唑啉（16 a），19 a - d，（R）-叔丁基- 3-（6-氟喹喔啉-2-基氧基）吡咯烷-1-羧酸酯（29）和35（IC 50 PDE10A
• Palladium-catalyzed direct Hiyama arylation of quinoxalin-2(1H)-ones with aryl siloxanes in water
  作者：Xinya Liu、Zhenwei Liu、Yingying Xue、Jingya Li、Dapeng Zou、Yangjie Wu、Yusheng Wu

  DOI：10.1016/j.tetlet.2020.152612

  日期：2020.12

  An efficient method for palladium-catalyzed direct Hiyama coupling of various quinoxalin-2(1H)-ones with aryl siloxanes has been developed. The protocol provides a convenient access to a variety of useful C3-arylated 1-methylquinoxalin-2(1H)-one derivatives in reasonable yields by using low cost water as a solvent and oxygen as an oxidant.

  已开发出一种有效的方法，用于钯催化的各种喹喔啉-2（1H）-与芳基硅氧烷的直接Hiyama偶联。该协议通过使用低成本的水作为溶剂和氧气作为氧化剂，以合理的产率方便地获得了各种有用的C3芳基化的1-甲基喹喔啉-2（1H）-衍生物。