6-methyl-1,2,3,4-tetrahydroquinoxalin-2-one | 148010-68-8

• 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
• 英文名称: 6-methyl-1,2,3,4-tetrahydroquinoxalin-2-one
• 英文别名: 5-methyl-3,4-dihydroquinoxalin-2(1H)-one；5-methyl-3,4-dihydro-1H-quinoxalin-2-one；5-Methyl-3,4-dihydro-1H-chinoxalin-2-on；1,2,3,4-Tetrahydro-5-methylquinoxalin-2-one；5-methyl-3,4-dihydro-1H-quinoxalin-2-one
• CAS: 148010-68-8
• 化学式: C₉H₁₀N₂O
• 分子量: 162.191
• InChiKey: CFQKMBGJKDUSKB-UHFFFAOYSA-N

物化性质

• 熔点：
  177-180 °C
• 沸点：
  357.2±42.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-methyl-1,2,3,4-tetrahydroquinoxalin-2-one 在 potassium tert-butylate 、 叔丁醇 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 Tert-butyl 6-methyl-4,5-dihydroimidazo[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：

  N-(2-methyl-6-nitrophenyl)glycine 在 乙醇 、 镍 作用下， 90.0 ℃ 、5.88 MPa 条件下， 生成 6-methyl-1,2,3,4-tetrahydroquinoxalin-2-one
  参考文献：
  名称：

  567.喹喔啉N-氧化物。第一部分。喹喔啉及其Bz取代衍生物的氧化

  摘要：

  DOI：

  10.1039/jr9530002816

文献信息

• A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones
  作者：Jaume Rostoll-Berenguer、Gonzalo Blay、M. Carmen Muñoz、José R. Pedro、Carlos Vila

  DOI：10.1021/acs.orglett.9b02157

  日期：2019.8.2

  An enantioselective photooxidative Mannich reaction of dihydroquinoxalinones with ketones by the merger of organophotoredox and asymmetric organocatalysis is described. This protocol features very mild reaction conditions using simple and cheap catalysts (Eosin Y and (S)-Proline) for the synthesis of chiral quinoxaline derivatives with good to high yields (up to 94%) and excellent enantioselectivities

  描述了通过有机光氧化还原和不对称有机催化的结合，二氢喹喔啉酮与酮的对映选择性光氧化曼尼希反应。该方案具有非常温和的反应条件，使用简单且廉价的催化剂（曙红Y和（S）-脯氨酸）合成手性喹喔啉衍生物，具有良好至高产率（高达94％）和出色的对映选择性（高达99％ee） 。
• 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。
• 4,5-cyclicimidazo[1,5-A]quinoxalines
  申请人：Pharmacia & Upjohn Company

  公开号：US05668282A1

  公开（公告）日：1997-09-16

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

  本发明揭示了不含内环羰基的咪唑[1,5-a]喹啉(I) ##STR1## 作为抗焦虑和镇静/催眠剂使用。
• 5,6-cyclicimidazo [1,5-a] Quinoxalines
  申请人：The Upjohn Company

  公开号：US05574038A1

  公开（公告）日：1996-11-12

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

  本发明揭示了不含内环羰基的咪唑并[1,5-a]喹啉(I) ##STR1## 作为抗焦虑和镇静/催眠剂。
• High-Affinity Partial Agonist Imidazo[1,5-<i>a</i>]quinoxaline Amides, Carbamates, and Ureas at the γ-Aminobutyric Acid A/Benzodiazepine Receptor Complex
  作者：E. Jon Jacobsen、Ruth E. TenBrink、Lindsay S. Stelzer、Kenneth L. Belonga、Donald B. Carter、Haesook K. Im、Wha Bin Im、Vimala H. Sethy、Andy H. Tang、Philip F. VonVoigtlander、James D. Petke

  DOI：10.1021/jm940765f

  日期：1996.1.1

  A series of imidazo[1,5-alpha]quinoxaline amides, carbamates, and ureas which have high affinity for the gamma-aminobutyric acid A/benzodiazepine receptor complex was developed. Compounds within this class have varying efficacies racing from antagonists to full agonists. However, most analogs were found to be partial agonists as indicated by [S-35]TBPS and Cl- current ratios. Many of these compounds were also effective in antagonizing metrazole-induced seizures in accordance with anticonvulsant and possible anxiolytic activity. Selected quinoxalines displayed limited benzodiazepine-type side effects such as ethanol potentiation and physical dependence in animal models. Dimethylamino urea 41 emerged as the most interesting analog, having a partial agonist profile in vitro while possessing useful activity in animal models of anxiety such as the Vogel and Geller assays. In accordance with its partial agonist profile, 41 was devoid of typical benzodiazepine side effects.