4-(2-fluoroethyl)-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide | 1210422-99-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 4-(2-fluoroethyl)-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 4-(2-Fluoroethyl)-7-(trifluoromethyl)-1lambda6,2,4-benzothiadiazine 1,1-dioxide；4-(2-fluoroethyl)-7-(trifluoromethyl)-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 1210422-99-3
• 化学式: C₁₀H₈F₄N₂O₂S
• 分子量: 296.245
• InChiKey: JYCRCQUYFDIKES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  58.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(2-fluoroethyl)-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide 在 sodium tetrahydroborate 作用下， 以 异丙醇 为溶剂， 反应 0.75h， 以75%的产率得到4-(2-fluoroethyl)-7-trifluoromethyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  New Fluorinated 1,2,4-Benzothiadiazine 1,1-Dioxides: Discovery of an Orally Active Cognitive Enhancer Acting through Potentiation of the 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors

  摘要：

  In the search of a potent cognitive enhancer, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxides have been synthesized and evaluated its positive allosteric modulators of the AMPA receptors. In the present work, we focused our efforts on the insertion of mono- or polyfluoro-substituted alkyl chains at the 4-position of the thiadiazine ring In all attempt to enhance the pharmacokinetic behavior of previously described compounds. Among all the described compounds, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxide, 12b, was shown to exert a strong activity on AMPA receptors in vitro and it marked cognitive-enhancing effect in vivo after oral administration to Wistar rats. Considering its in vivo activity, the metabolic degradation of 12b was studied and compared to that of its nonfluorinated analogue 9b. Taken together, results of this study clearly validated the positive impact of the fluorine atom on the alkyl chain at file 4-position of benzothiadiazine dioxides oil activity and metabolic stability.

  DOI：

  10.1021/jm901495t
• 作为产物：
  描述：

  1-氟-2-碘乙烷 、 7-trifluoromethyl-4H-1,2,4-benzothiadiazine1,1-dioxide 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 30.0h， 以61%的产率得到4-(2-fluoroethyl)-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  New Fluorinated 1,2,4-Benzothiadiazine 1,1-Dioxides: Discovery of an Orally Active Cognitive Enhancer Acting through Potentiation of the 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors

  摘要：

  In the search of a potent cognitive enhancer, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxides have been synthesized and evaluated its positive allosteric modulators of the AMPA receptors. In the present work, we focused our efforts on the insertion of mono- or polyfluoro-substituted alkyl chains at the 4-position of the thiadiazine ring In all attempt to enhance the pharmacokinetic behavior of previously described compounds. Among all the described compounds, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxide, 12b, was shown to exert a strong activity on AMPA receptors in vitro and it marked cognitive-enhancing effect in vivo after oral administration to Wistar rats. Considering its in vivo activity, the metabolic degradation of 12b was studied and compared to that of its nonfluorinated analogue 9b. Taken together, results of this study clearly validated the positive impact of the fluorine atom on the alkyl chain at file 4-position of benzothiadiazine dioxides oil activity and metabolic stability.

  DOI：

  10.1021/jm901495t

文献信息

• New Fluorinated 1,2,4-Benzothiadiazine 1,1-Dioxides: Discovery of an Orally Active Cognitive Enhancer Acting through Potentiation of the 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors
  作者：Pierre Francotte、Eric Goffin、Pierre Fraikin、Pierre Lestage、Jean-Claude Van Heugen、Florian Gillotin、Laurence Danober、Jean-Yves Thomas、Patrice Chiap、Daniel-Henri Caignard、Bernard Pirotte、Pascal de Tullio

  DOI：10.1021/jm901495t

  日期：2010.2.25

  In the search of a potent cognitive enhancer, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxides have been synthesized and evaluated its positive allosteric modulators of the AMPA receptors. In the present work, we focused our efforts on the insertion of mono- or polyfluoro-substituted alkyl chains at the 4-position of the thiadiazine ring In all attempt to enhance the pharmacokinetic behavior of previously described compounds. Among all the described compounds, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxide, 12b, was shown to exert a strong activity on AMPA receptors in vitro and it marked cognitive-enhancing effect in vivo after oral administration to Wistar rats. Considering its in vivo activity, the metabolic degradation of 12b was studied and compared to that of its nonfluorinated analogue 9b. Taken together, results of this study clearly validated the positive impact of the fluorine atom on the alkyl chain at file 4-position of benzothiadiazine dioxides oil activity and metabolic stability.