7-Chlor-4-ethyl-1,2,4-benzothiadiazin-1,1-dioxid | 38443-11-7

• 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: 7-Chlor-4-ethyl-1,2,4-benzothiadiazin-1,1-dioxid
• 英文别名: 7-chloro-4-ethyl-4H-benzo[e][1,2,4]thiadiazine 1,1-dioxide；7-Chloro-4-ethyl-1lambda6,2,4-benzothiadiazine 1,1-dioxide；7-chloro-4-ethyl-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 38443-11-7
• 化学式: C₉H₉ClN₂O₂S
• 分子量: 244.702
• InChiKey: ZUWSZVDLWBTEAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-Chlor-4-ethyl-1,2,4-benzothiadiazin-1,1-dioxid 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 3.75h， 生成 7-chloro-4-ethyl-2-methyl-3H-1lambda6,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Design, Synthesis, and Pharmacology of Novel 7-Substituted 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides as Positive Allosteric Modulators of AMPA Receptors

  摘要：

  A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the 7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current in rat cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration.

  DOI：

  10.1021/jm070120i
• 作为产物：
  描述：

  2-氨基-5-氯苯磺酰胺 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 7-Chlor-4-ethyl-1,2,4-benzothiadiazin-1,1-dioxid
  参考文献：
  名称：

  Design, Synthesis, and Pharmacology of Novel 7-Substituted 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides as Positive Allosteric Modulators of AMPA Receptors

  摘要：

  A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the 7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current in rat cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration.

  DOI：

  10.1021/jm070120i

文献信息

• Synthesis and Pharmacology of Mono-, Di-, and Trialkyl-Substituted 7-Chloro-3,4-dihydro-2<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxides Combined with X-ray Structure Analysis to Understand the Unexpected Structure–Activity Relationship at AMPA Receptors
  作者：Anja Probst Larsen、Pierre Francotte、Karla Frydenvang、Daniel Tapken、Eric Goffin、Pierre Fraikin、Daniel-Henri Caignard、Pierre Lestage、Laurence Danober、Bernard Pirotte、Jette Sandholm Kastrup

  DOI：10.1021/acschemneuro.5b00318

  日期：2016.3.16

  4-monoalkyl-substituted benzothiadiazine dioxides for which the cyclopropyl group constitutes the best choice of substituent. 7b was subjected to X-ray structural analysis in complex with the GluA2 ligand-binding domain. We propose an explanation of the unexpected structure–activity relationship of this new series of mono-, di-, and trialkyl-substituted 1,2,4-benzothiadiazine 1,1-dioxide compounds. The

  2-氨基-3-（3-羟基-5-甲基异恶唑-4-基）丙酸（AMPA）型离子型谷氨酸受体的正构构调节剂是用于治疗神经系统疾病（例如阿尔茨海默氏病）的有前途的化合物。在这里，我们报告一系列单，二或三烷基取代的7-氯-3,4-二氢-2 H -1,2,4-苯并噻二嗪1,1-二氧化物的合成和药理学评估，其中包括总共16个新的调制器。三取代的化合物7b，7d和7e表现出有效的活性（EC 2x= 2.7–4.3μM；在体外细胞荧光测定（FLIPR）中作为AMPA受体增强剂的，负责AMPA介导的应答增加2倍的化合物的浓度。与先前描述的4-单烷基取代的苯并噻二二嗪二氧化物相反，4-环丙基化合物7f的效力明显较低（EC 2x = 60μM），其中环丙基是取代基的最佳选择。7b将其与GluA2配体结合结构域一起进行X射线结构分析。我们提出了这种新的单，二和三烷基取代的1,2,4-苯并噻二嗪1,1-二氧化物化合物系