2-Amino-6-methyl-4-oxo-4H-3,1-benzothiazin | 131357-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 2-Amino-6-methyl-4-oxo-4H-3,1-benzothiazin
• 英文别名: 2-amino-6-methyl-4H-3,1-benzothiazin-4-one；2-Amino-6-methyl-3,1-benzothiazin-4-one
• CAS: 131357-75-0
• 化学式: C₉H₈N₂OS
• 分子量: 192.241
• InChiKey: DHEFASNXPZZXAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲基苯甲酰基异硫氰酸酯 、 2-Amino-6-methyl-4-oxo-4H-3,1-benzothiazin 以 丙酮 为溶剂， 反应 3.0h， 以31%的产率得到4-methyl-N-[(6-methyl-4-oxo-3,1-benzothiazin-2-yl)carbamothioyl]benzamide
  参考文献：
  名称：

  衍生自取代的芳硫基脲的新型杂环：3，1-苯并噻嗪-4-酮，噻吩并[3,2- d ] [1,3]噻嗪-4-酮和1,2,4-噻二唑[2,3-]的合成a ] [3,1]苯并噻嗪-5-酮

  摘要：

  已经制备了一系列杂环芳基硫脲并作为闭环反应的起始原料进行了研究。据报道（通过环缩合反应）形成了几个新的3,1-苯并噻嗪-4-酮和噻吩并[3,2- d ] [1,3]噻嗪-4-酮。进行氧化环化反应生成苯并噻唑-4-羧酸甲酯（通过形成SC键）以及1,2,4-噻二唑-[2,3- a ] [3,1]苯并噻嗪-5-酮（通过形成S N键）。

  DOI：

  10.1002/jhet.5570330225
• 作为产物：
  描述：

  Methyl 2-(carbamothioylamino)-5-methylbenzoate 在 硫酸 、 水 作用下， 反应 4.0h， 以78%的产率得到2-Amino-6-methyl-4-oxo-4H-3,1-benzothiazin
  参考文献：
  名称：

  Dual Targeting of Adenosine A_2A Receptors and Monoamine Oxidase B by 4H-3,1-Benzothiazin-4-ones

  摘要：

  Blockade of A(2A) adenosine receptors (A(2A)ARs) and inhibition of monoamine oxidase B (MAO-B) in the brain are considered attractive strategies for the treatment of neurodegenerative diseases such as Parkinson's disease (PD). In the present study, benzothiazinones, e.g., 2-(3-chlorophenoxy)-N-(4-oxo-4H-3,1-benzothiazin-2-yl)acetamide (13), were identified as a novel class of potent MAO-B inhibitors (IC50 human MAO-B: 1.63 nM). Benzothiazinones with large substituents in the 2-position, e.g., methoxycinnamoylamino, phenylbutyrylamino, or chlorobenzylpiperazinylbenzamido residues (14, 17, 27, and 28), showed high affinity and selectivity for A(2A)ARs (K-i human A(2A)AR: 39.5-69.5 nM). By optimizing benzothiazinones for both targets, the first potent, dual-acting A(2A)AR/MAO-B inhibitors with a nonxanthine structure were developed. The best derivative was N-(4-oxo-4H-3,1-benzothiazin-2-yl)-4-phenylbutanamide (17, K-i human A(2A), 39.5 nM; IC50 human MAO-B, 34.9 nM; selective versus other AR subtypes and MAO-A), which inhibited A(2A)AR-induced cAMP accumulation and showed competitive, reversible MAO-B inhibition. The new compounds may be useful tools for validating the A(2A)AR/MAO-B dual target approach in PD.

  DOI：

  10.1021/jm400336x

文献信息

• Mehrcyclische Azine mit Heteroatomen in 1- und 3-Stellung, 25. Mitt.: 2-Amino-4-oxo-4H-3,1-benzothiazine: Darstellung,Dimroth-Umlagerung zu 4-Oxo-2-thioxo-1,2,3,4-tetrahydrochinazolinen und MS/MS-Fragmentierung
  作者：Siegfried Leistner、Michael Gütschow、Joachim Stach

  DOI：10.1002/ardp.19903231009

  日期：——

  2‐Amino‐4‐oxo‐4H‐3,1‐benzothiazinen 4a–c. Entgegen Literaturangaben geben 1 oder 2 unter anderen Reaktionsbedingungen durch Cyclokondensation die 2‐Benzoylamino‐4‐oxo‐4H‐3,1‐benzothiazine 6a–c. Dimroth‐Umlagerung von 4 führt zu den 2‐Thioxochinazolinen 5. Die ms Fragmentierung von 4, 5 und 6 wird diskutiert.

  苯甲酰硫脲衍生物 1-3 与浓反应。H2SO4 到 2-amino-4-oxo-4H-3,1-benzothiazines 4a – c。与文献相反，1 或 2 在不同反应条件下通过环缩合反应得到 2-苯甲酰氨基-4-氧代-4H-3,1-苯并噻嗪 6a-c。4 的 Dimroth 重排导致 2- thioxoquinazolines 5。讨论了 4、5 和 6 的 ms 碎裂。
• Dual Targeting of Adenosine A_2A Receptors and Monoamine Oxidase B by 4<i>H</i>-3,1-Benzothiazin-4-ones
  作者：Anne Stößel、Miriam Schlenk、Sonja Hinz、Petra Küppers、Jag Heer、Michael Gütschow、Christa E. Müller

  DOI：10.1021/jm400336x

  日期：2013.6.13

  Blockade of A(2A) adenosine receptors (A(2A)ARs) and inhibition of monoamine oxidase B (MAO-B) in the brain are considered attractive strategies for the treatment of neurodegenerative diseases such as Parkinson's disease (PD). In the present study, benzothiazinones, e.g., 2-(3-chlorophenoxy)-N-(4-oxo-4H-3,1-benzothiazin-2-yl)acetamide (13), were identified as a novel class of potent MAO-B inhibitors (IC50 human MAO-B: 1.63 nM). Benzothiazinones with large substituents in the 2-position, e.g., methoxycinnamoylamino, phenylbutyrylamino, or chlorobenzylpiperazinylbenzamido residues (14, 17, 27, and 28), showed high affinity and selectivity for A(2A)ARs (K-i human A(2A)AR: 39.5-69.5 nM). By optimizing benzothiazinones for both targets, the first potent, dual-acting A(2A)AR/MAO-B inhibitors with a nonxanthine structure were developed. The best derivative was N-(4-oxo-4H-3,1-benzothiazin-2-yl)-4-phenylbutanamide (17, K-i human A(2A), 39.5 nM; IC50 human MAO-B, 34.9 nM; selective versus other AR subtypes and MAO-A), which inhibited A(2A)AR-induced cAMP accumulation and showed competitive, reversible MAO-B inhibition. The new compounds may be useful tools for validating the A(2A)AR/MAO-B dual target approach in PD.
• Novel heterocycles derived from substituted aroylthioureas: Synthesis of 3, l-benzothiazin-4-ones, thieno[3,2-<i>d</i>][1,3]thiazin-4-ones and 1,2,4-thiadiazolo[2,3-<i>a</i>][3,1]benzothiazin-5-ones
  作者：M. Gütschow

  DOI：10.1002/jhet.5570330225

  日期：1996.3

  A series of heterocyclic aroylthioureas has been prepared and investigated as starting materials for ring closure reactions. The formation of several new 3,1-benzothiazin-4-ones and thieno[3,2-d][1,3]thiazin-4-ones (via cyclocondensation reactions) is reported. Oxidative cyclizations were carried out to produce methyl benzothiazole-4-carboxylates (via formation of an S-C bond) as well as 1,2,4-thiadiazolo-[2

  已经制备了一系列杂环芳基硫脲并作为闭环反应的起始原料进行了研究。据报道（通过环缩合反应）形成了几个新的3,1-苯并噻嗪-4-酮和噻吩并[3,2- d ] [1,3]噻嗪-4-酮。进行氧化环化反应生成苯并噻唑-4-羧酸甲酯（通过形成SC键）以及1,2,4-噻二唑-[2,3- a ] [3,1]苯并噻嗪-5-酮（通过形成S N键）。