7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine-1,1-dioxide

• 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-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine-1,1-dioxide
• 英文别名: 7-Chloro-3-(1,1-dimethylpropyl)amino-4h-1,2,4-benzothiadiazine-1,1-dioxide；7-chloro-N-(2-methylbutan-2-yl)-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-imine
• 化学式: C₁₂H₁₆ClN₃O₂S
• 分子量: 301.797
• InChiKey: RLHBDBWDXYRDOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-chloro-2,3-dihydro-3-oxo-4H-1,2,4-benzothiadiazine 在 吡啶 、 sodium hydroxide 、 tetraphosphorus decasulfide 、 溴 、 碳酸氢钠 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 6.17h， 生成 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

文献信息

• Intranasal administration of modulators of hypothalamic ATP-sensitive potassium channels
  申请人：Herlands Louis

  公开号：US20070026079A1

  公开（公告）日：2007-02-01

  Provided are methods of increasing K ATP channel activity in the hypothalamus of a mammal, methods of reducing glucose production in a mammal, methods of reducing peripheral glucose levels in a mammal, methods of reducing triglyceride levels in a mammal, methods of reducing very low density lipoprotein (VLDL) levels in a mammal, methods of methods of reducing gluconeogenesis in the liver of a mammal, methods of treating metabolic disorders such as diabetes, hyperglycemia, insulin resistance, glucose intolerance, metabolic syndrome and/or obesity, and methods of increasing glucose production and peripheral glucose levels in a mammal. Also provided are methods of treating heart failure, ischemia, coronary heart disease, familial lipoprotein lipase deficiency, hypopituitarism, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, atherosclerosis, hypercholesterolemia, hypertension, polycystic ovary syndrome, gonadotropin deficiency and/or amenorrhea.
• Modulation of Hypothalamic Atp-Sensitive Potassium Channels
  申请人：Rossetti Luciano

  公开号：US20090012067A1

  公开（公告）日：2009-01-08

  Provided are methods of increasing K ATP activity in the hypothalamus of a mammal, methods of reducing glucose production and peripheral blood glucose levels in a mammal, methods of inhibiting gluconeogenesis in the liver of a mammal, and methods of increasing glucose production and peripheral blood glucose levels in a mammal.
• 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.