7-iodo-3-thioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide | 579510-15-9

• 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-iodo-3-thioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 7-iodo-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazine-3-thione；7-iodo-1,1-dioxo-4H-1λ6,2,4-benzothiadiazine-3-thione
• CAS: 579510-15-9
• 化学式: C₇H₅IN₂O₂S₂
• 分子量: 340.165
• InChiKey: FZOKNPAVPXMLSN-UHFFFAOYSA-N

物化性质

• 熔点：
  219-222 °C
• 沸点：
  477.7±47.0 °C(Predicted)
• 密度：
  2.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-iodo-3-thioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 4.0h， 生成 7-iodo-3-cyclobutylamino-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：

  对碘苯胺 在 吡啶 、 三氯化铝 、 tetraphosphorus decasulfide 作用下， 以 硝基甲烷 为溶剂， 反应 4.0h， 生成 7-iodo-3-thioxo-3,4-dihydro-2H-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

• 1,4,2-Benzo/pyridodithiazine 1,1-Dioxides Structurally Related to the ATP-Sensitive Potassium Channel Openers 1,2,4-Benzo/pyridothiadiazine 1,1-Dioxides Exert a Myorelaxant Activity Linked to a Distinct Mechanism of Action
  作者：Bernard Pirotte、Pascal de Tullio、Xavier Florence、Eric Goffin、Fabian Somers、Stéphane Boverie、Philippe Lebrun

  DOI：10.1021/jm301743b

  日期：2013.4.25

  The synthesis of diversely substituted 3-alkyl/aralkyl/arylamino-1,4,2-benzodithiazine 1,1-dioxides and 3-alkylaminopyrido[4,3-e]-1,4,2-dithiazine 1,1-dioxides is described. Their biological activities on pancreatic β-cells and on smooth muscle cells were compared to those of the reference ATP-sensitive potassium channel (KATP channel) openers diazoxide and 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine

  各种取代的3-烷基/芳烷基/芳基氨基-1,4,2-苯并噻二嗪1,1-二氧化物和3-烷基氨基吡啶并[4,3 - e ] -1,4,2-二噻嗪1,1-二氧化物的合成是描述。将它们在胰腺β细胞和平滑肌细胞上的生物学活性与参考ATP敏感钾通道（K ATP通道）开放剂二叠氮和7-氯-3-异丙基氨基-4 H的生物学活性进行了比较。-1,2,4-苯并噻二嗪1,1-二氧化物 目的是评估用等规的1,4,2-二噻嗪环取代1,2,4-噻二嗪环对生物活性的影响。尽管一些在3-位带有1-苯基乙基氨基侧链的化合物发挥了显着的肌松活性，但发现大多数二噻嗪类似物在胰腺组织上是无活性的。这种作用似乎与K ATP通道的开放无关，而是反映了与钙通道阻滞剂相似的作用机制。还发现紧密相关的3-（1-苯乙基）硫烷基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物由于K ATP均具有显着的髓鞘舒张活性。通道激活和钙通道阻滞剂机制。本工作强调了在K