N-(4-oxo-4H-thieno[3,2-d][1,3]thiazin-2-yl)-4-phenylbutanamide | 1439489-07-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(4-oxo-4H-thieno[3,2-d][1,3]thiazin-2-yl)-4-phenylbutanamide
• 英文别名: N-(4-oxothieno[3,2-d][1,3]thiazin-2-yl)-4-phenylbutanamide
• CAS: 1439489-07-2
• 化学式: C₁₆H₁₄N₂O₂S₂
• 分子量: 330.431
• InChiKey: PTIAQKMBSAVDRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-苯基丁酸 在 N-甲基吗啉 、 吡啶 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.0h， 生成 N-(4-oxo-4H-thieno[3,2-d][1,3]thiazin-2-yl)-4-phenylbutanamide
  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