7-methoxy-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide | 228253-50-7

• 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-methoxy-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 7-Methoxy-3-(methylthio)-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide；7-methoxy-3-methylsulfanyl-4H-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 228253-50-7
• 化学式: C₉H₁₀N₂O₃S₂
• 分子量: 258.322
• InChiKey: FVYXYCUVBYAEHU-UHFFFAOYSA-N

物化性质

• 熔点：
  270-276 °C
• 沸点：
  463.2±47.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-methoxy-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide 在 间氯过氧苯甲酸 作用下， 以 丙酮 为溶剂， 生成 N-cyclobutyl-7-methoxy-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazin-3-imine
  参考文献：
  名称：

  Synthesis and evaluation of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives as KATP channel agonists

  摘要：

  A series of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives has been synthesized and evaluated as K-ATP channel agonists using the inside-out excised patch clamp technique. The most active compounds were similar to20-fold more potent than diazoxide in opening K-ATP channels. A linear relationship exists between the potency of the compound and the sigma value of the 7-substituent with electron-withdrawing groups exhibiting higher activity. These compounds may be useful in modulating insulin release from pancreatic beta-cells and in diseases associated with hyperinsulinemia. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00617-0
• 作为产物：
  描述：

  7-甲氧基-1,1-二氧代-1,4-二氢-2H- 1lambda*6*-苯并[1,2,4]噻二嗪-3-酮 在 吡啶 、 diphosphorus pentasulfide 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 3.5h， 生成 7-methoxy-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  对K（ATP）通道活化特性和4H-1,2,4-苯并噻二嗪1,1-二氧化物7位和3位上取代基的性质的组织选择性的影响。

  摘要：

  本工作探讨了在7位上不同取代的3-烷基氨基-4H-1,2,4-苯并噻二嗪1,1-二氧化物。那些与先前描述的钾通道开放剂（例如二氧化苯并噻二嗪BPDZ 73）在结构上相关的化合物已在胰腺内分泌组织和血管平滑肌组织上作为推定的K（ATP）通道活化剂进行了测试。在7位引入的取代基的性质以及在3位引入的烷基氨基侧链的性质强烈影响4H-1,2,4-苯并噻二嗪1,1-二氧化物的效能和组织选择性。因此，在7位上带有甲基或甲氧基或在该位置上没有取代基并带有乙基，异丙基的化合物，发现3-位的环丁基或环丁基氨基是有效的和选择性的胰岛素从大鼠胰腺B细胞（即10a，10b，12b，12d，22c）释放的抑制剂。相反，3-烷基氨基-7-三氟甲基-（20a-c）和3-烷基氨基-7-戊基-4H-1,2,4-苯并噻二嗪1,1-二氧化物（11a，b）在表面上表现出明显的肌松活性。大鼠主动脉环。在后一种化合物中，3-烷基氨基

  DOI：

  10.1021/jm0311339

文献信息

• Hydroxylated Analogues of ATP-Sensitive Potassium Channel Openers Belonging to the Group of 6- and/or 7-Substituted 3-Isopropylamino-4<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxides: Toward an Improvement in Sulfonylurea Receptor 1 Selectivity and Metabolism Stability
  作者：Pascal de Tullio、Anne-Catherine Servais、Marianne Fillet、Florian Gillotin、Fabian Somers、Patrice Chiap、Philippe Lebrun、Bernard Pirotte

  DOI：10.1021/jm200786z

  日期：2011.12.22

  Diversely substituted 3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides are known to be potent K-ATP channel openers, with several drugs being selective for the SUR1/Kir6.2 channel subtype. This work examined the biological activity, tissue selectivity, and in vitro metabolic stability of hydroxylated analogues of 3-isopropylaminobenzothiadiazine dioxides. Because of the presence of a chiral center, the R and S isomers were prepared separately and characterized. R isomers were systematically found to be more potent and more selective than S isomers on pancreatic tissue (compared to vascular smooth muscle tissue), leading to compounds with an improved sulfonylurea receptor 1 (SUR1) selectivity. An in vitro metabolic study revealed that 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (1a) was rapidly biotransformed and led in part to a mixture of the corresponding (R)- and (S)-3-(1-hydroxy-2-propyl)amino-substituted derivatives. Radioisotopic experiments characterized one of the most potent and SUR1-selective enantiomers, (R)-7-chloro-3-(1-hydroxy-2-propyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide 13a, as being a K-ATP channel opener. Moreover, 13a exhibited an enhanced metabolic stability. Such a compound can be considered as a new lead candidate displaying improved physicochemical (hydrosolubility) and pharmacological (tissue selectivity) properties as well as improved metabolic stability compared to its nonhydroxylated counterpart, 1a.