7-chloro-3-(methylsulfinyl)-4H-1,2,4-benzothiadiazine 1,1-dioxide | 64670-67-3

• 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: 7-chloro-3-(methylsulfinyl)-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 7-chloro-3-methylsulfinyl-4H-1,2,4-benzothiadiazine 1,1-dioxide；7-chloro-3-methylsulfinyl-4H-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 64670-67-3
• 化学式: C₈H₇ClN₂O₃S₂
• 分子量: 278.74
• InChiKey: SDBBSZRUKMBDEO-UHFFFAOYSA-N

物化性质

• 熔点：
  260-261 °C
• 沸点：
  525.8±52.0 °C(Predicted)
• 密度：
  1.83±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  叔戊基胺 、 7-chloro-3-(methylsulfinyl)-4H-1,2,4-benzothiadiazine 1,1-dioxide 反应 2.0h， 以40%的产率得到7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine-1,1-dioxide
  参考文献：
  名称：

  Toward Tissue-Selective Pancreatic B-Cells K_ATP Channel Openers Belonging to 3-Alkylamino-7-halo-4H-1,2,4-benzothiadiazine 1,1-Dioxides

  摘要：

  3-(Alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides were synthesized, and their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the K-ATP channel activators diazoxide and pinacidil. Structure-activity relationships indicated that an improved potency and selectivity for the pancreatic tissue was obtained by introducing a fluorine atom in the 7-position and a short linear (preferably ethyl) or cyclic (preferably cyclobutyl) hydrocarbon chain on the nitrogen atom in the 3-position. By contrast, strong myorelaxant activity was gained by the introduction of a halogen atom different from the fluorine atom in the 7-position and a bulky branched alkylamino chain in the 3-position. Thus, 3-(ethylamino)-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide (11) expressed a marked inhibitory activity on pancreatic B-cells (IC50 = 1 muM) associated with a weak vasorelaxant effect (ED50 > 300 muM), whereas 7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide (27), which was only slightly active on insulin-secreting cells (IC50 > 10 muM), was found to be very potent on vascular smooth muscle cells (ED50 = 0.29 muM). Radioisotopic and electrophysiological. investigations performed with 7-chlorinated, 7-iodinated, and 7-fluorinated 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides confirmed that the drugs activated K-ATP channels. The present data revealed that subtle structural modifications of 3-(alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides can generate original compounds activating K-ATP channels and exhibiting different in vitro tissue selectivity profiles.

  DOI：

  10.1021/jm021117w
• 作为产物：
  描述：

  7-chloro-2,3-dihydro-3-oxo-4H-1,2,4-benzothiadiazine 在 吡啶 、 tetraphosphorus decasulfide 、 溴 、 碳酸氢钠 、 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 生成 7-chloro-3-(methylsulfinyl)-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Effect on insulin release of compounds structurally related to the potassium-channel opener 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (BPDZ 73): introduction of heteroatoms on the 3-alkylamino side chain of the benzothiadiazine 1,1-dioxide ring

  摘要：

  7-氯-3-吡啶基（烷基）氨基-4H-1,2,4-苯并噻二嗪-1,1-二氧化物和3-烷基氨基-7-氯-4H-1,2,4-苯并噻二嗪-1,1-二氧化物，其侧链在3位含有一个或多个杂原子，已经合成，以寻找新的有效的KATP通道开放剂。通过测量它们对胰岛素释放过程的抑制活性，将这些化合物作为潜在的胰岛B细胞KATP通道开放剂进行了测试。讨论了3位侧链性质对生物活性的影响。

  DOI：

  10.1211/0022357011776216

文献信息

• 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。
• US6242443B1
  申请人：——

  公开号：US6242443B1

  公开（公告）日：2001-06-05
• Toward Tissue-Selective Pancreatic B-Cells K_ATP Channel Openers Belonging to 3-Alkylamino-7-halo-4<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxides
  作者：Pascal de Tullio、Bénédicte Becker、Stéphane Boverie、Michael Dabrowski、Philip Wahl、Marie-Hélène Antoine、Fabian Somers、Sophie Sebille、Raogo Ouedraogo、John Bondo Hansen、Philippe Lebrun、Bernard Pirotte

  DOI：10.1021/jm021117w

  日期：2003.7.1

  3-(Alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides were synthesized, and their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the K-ATP channel activators diazoxide and pinacidil. Structure-activity relationships indicated that an improved potency and selectivity for the pancreatic tissue was obtained by introducing a fluorine atom in the 7-position and a short linear (preferably ethyl) or cyclic (preferably cyclobutyl) hydrocarbon chain on the nitrogen atom in the 3-position. By contrast, strong myorelaxant activity was gained by the introduction of a halogen atom different from the fluorine atom in the 7-position and a bulky branched alkylamino chain in the 3-position. Thus, 3-(ethylamino)-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide (11) expressed a marked inhibitory activity on pancreatic B-cells (IC50 = 1 muM) associated with a weak vasorelaxant effect (ED50 > 300 muM), whereas 7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide (27), which was only slightly active on insulin-secreting cells (IC50 > 10 muM), was found to be very potent on vascular smooth muscle cells (ED50 = 0.29 muM). Radioisotopic and electrophysiological. investigations performed with 7-chlorinated, 7-iodinated, and 7-fluorinated 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides confirmed that the drugs activated K-ATP channels. The present data revealed that subtle structural modifications of 3-(alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides can generate original compounds activating K-ATP channels and exhibiting different in vitro tissue selectivity profiles.
• Effect on insulin release of compounds structurally related to the potassium-channel opener 7-chloro-3-isopropylamino-4<i>H</i>-1,2,4-benzothiadiazine 1,1-dioxide (BPDZ 73): introduction of heteroatoms on the 3-alkylamino side chain of the benzothiadiazine 1,1-dioxide ring
  作者：S Boverie、M-H Antoine、P de Tullio、F Somers、B Becker、S Sebille、P Lebrun、B Pirotte

  DOI：10.1211/0022357011776216

  日期：2010.2.18

  7-Chloro-3-pyridyl(alkyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxides and 3-alkylamino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides containing one or more heteroatoms on the side chain in the 3 position have been synthesized in an attempt to discover new potent KATP-channel openers. The compounds were tested as putative pancreatic B-cells KATP channel openers by measuring their inhibitory activity on the insulin releasing process. The influence on the biological activity of the nature of the side chain in the 3 position is discussed.

  7-氯-3-吡啶基（烷基）氨基-4H-1,2,4-苯并噻二嗪-1,1-二氧化物和3-烷基氨基-7-氯-4H-1,2,4-苯并噻二嗪-1,1-二氧化物，其侧链在3位含有一个或多个杂原子，已经合成，以寻找新的有效的KATP通道开放剂。通过测量它们对胰岛素释放过程的抑制活性，将这些化合物作为潜在的胰岛B细胞KATP通道开放剂进行了测试。讨论了3位侧链性质对生物活性的影响。