6,7-difluoro-3-(1H-imidazol-1-yl)-4H-1,2,4-benzothiadiazine 1,1-dioxide | 201224-80-8

• 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: 6,7-difluoro-3-(1H-imidazol-1-yl)-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 6,7-Difluoro-3-(imidazol-1-yl)-4H-1,2,4-benzothiadiazine 1,1-dioxide；6,7-difluoro-3-imidazol-1-yl-4H-1lambda6,2,4-benzothiadiazine 1,1-dioxide；6,7-difluoro-3-imidazol-1-yl-4H-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 201224-80-8
• 化学式: C₁₀H₆F₂N₄O₂S
• 分子量: 284.246
• InChiKey: BXXUKZBNPXLAMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  84.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6,7-difluoro-3-(1H-imidazol-1-yl)-4H-1,2,4-benzothiadiazine 1,1-dioxide 、 环丁基胺 以 1,4-二氧六环 为溶剂， 反应 8.0h， 以45%的产率得到N-cyclobutyl-3-cyclobutylimino-7-fluoro-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazin-6-amine
  参考文献：
  名称：

  3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-Dioxides as ATP-Sensitive Potassium Channel Openers:  Effect of 6,7-Disubstitution on Potency and Tissue Selectivity

  摘要：

  A series of 6,7-disubstituted 4H-1,2,4-benzothiadiazine 1,1-dioxides bearing a short alkylamino side chain in the 3-position were synthesized. These compounds were tested on rat pancreatic islets and on rat aorta rings. In vitro data indicated that in most cases substitution in the 6 and the 7 positions increased their activity as inhibitors of insulin secretion, while the myorelaxant potency of the drugs was maintained or enhanced according to the nature of the substituent in the 7-position. The presence of either chlorine or bromine atoms in the 6 and 7 positions did not improve the apparent selectivity of the drugs for the pancreatic tissue. By contrast, the introduction of one or two fluorine atoms, as well as the presence of a methoxy group in the 7-position, generated potent and selective inhibitors of insulin release. Radioisotopic and fluorimetric experiments performed with the most potent compound inhibiting insulin release (34, BPDZ 259, 6-chloro-7-fluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide) confirmed that the drug activated K-ATP channels. 34 was found to be one of the most potent and selective pancreatic potassium channel openers yet described.

  DOI：

  10.1021/jm0580050
• 作为产物：
  描述：

  2-amino-4,5-difluorobenzenesulfonamide 生成 6,7-difluoro-3-(1H-imidazol-1-yl)-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  1,2,4-benzothiadiazine derivatives, their preparation and use

  摘要：

  1,2,4-苯并噻二嗪衍生物的化学式如下： 其中D，R1，R2，R3，R4，R5，R12，R13，R14，R15在描述中有定义，描述了其组成以及制备该化合物的方法。 这些化合物在治疗中枢神经系统、心血管系统、呼吸系统、消化系统和内分泌系统疾病方面具有用途。

  公开号：

  US06242443B1

文献信息

• US6242443B1
  申请人：——

  公开号：US6242443B1

  公开（公告）日：2001-06-05
• 3-Alkylamino-4<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxides as ATP-Sensitive Potassium Channel Openers:  Effect of 6,7-Disubstitution on Potency and Tissue Selectivity
  作者：Pascal de Tullio、Stéphane Boverie、Bénédicte Becker、Marie-Hélène Antoine、Quynh-Anh Nguyen、Pierre Francotte、Stéphane Counerotte、Sophie Sebille、Bernard Pirotte、Philippe Lebrun

  DOI：10.1021/jm0580050

  日期：2005.7.1

  A series of 6,7-disubstituted 4H-1,2,4-benzothiadiazine 1,1-dioxides bearing a short alkylamino side chain in the 3-position were synthesized. These compounds were tested on rat pancreatic islets and on rat aorta rings. In vitro data indicated that in most cases substitution in the 6 and the 7 positions increased their activity as inhibitors of insulin secretion, while the myorelaxant potency of the drugs was maintained or enhanced according to the nature of the substituent in the 7-position. The presence of either chlorine or bromine atoms in the 6 and 7 positions did not improve the apparent selectivity of the drugs for the pancreatic tissue. By contrast, the introduction of one or two fluorine atoms, as well as the presence of a methoxy group in the 7-position, generated potent and selective inhibitors of insulin release. Radioisotopic and fluorimetric experiments performed with the most potent compound inhibiting insulin release (34, BPDZ 259, 6-chloro-7-fluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide) confirmed that the drug activated K-ATP channels. 34 was found to be one of the most potent and selective pancreatic potassium channel openers yet described.
• 1,2,4-benzothiadiazine derivatives, their preparation and use
  申请人：Novo Nordisk AIS

  公开号：US06242443B1

  公开（公告）日：2001-06-05

  1,2,4-Benzothiadiazine derivatives represented by formula wherein D, R1, R2, R3, R4, R5, R12, R13, R14, R15 are defined in the description, composition thereof and methods for preparing the compounds are described. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

  1,2,4-苯并噻二嗪衍生物的化学式如下： 其中D，R1，R2，R3，R4，R5，R12，R13，R14，R15在描述中有定义，描述了其组成以及制备该化合物的方法。 这些化合物在治疗中枢神经系统、心血管系统、呼吸系统、消化系统和内分泌系统疾病方面具有用途。