7-chloro-5-ethyl-3-methyl-3,4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide | 194020-01-4

• 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-5-ethyl-3-methyl-3,4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide
• 英文别名: 7-chloro-5-ethyl-3-methyl-3,4-dihydro-2H-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 194020-01-4
• 化学式: C₁₀H₁₃ClN₂O₂S
• 分子量: 260.744
• InChiKey: DPJNGQJOTVRIPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  66.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-chloro-5-ethyl-3-methyl-3,4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide 在 sodium cyanoborohydride 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以65%的产率得到5-chloro-3-ethyl-2-(ethylamino)benzenesulfonamide
  参考文献：
  名称：

  硼氢化物对3-取代的2,3-二氢苯并噻二嗪的区域选择性还原

  摘要：

  基于在不同溶剂中用NaBH 3 CN进行区域选择性还原，开发了一种N-1或N-2烷基取代的2-氨基苯磺酰胺的简单有效的合成途径。

  DOI：

  10.1016/j.tetlet.2010.06.081
• 作为产物：
  描述：

  2-乙基苯胺 在 N-氯代丁二酰亚胺 、 三氯化铝 、 3 A molecular sieve 、 硫酸 、 camphor-10-sulfonic acid 作用下， 以 水 、 乙腈 为溶剂， 反应 17.75h， 生成 7-chloro-5-ethyl-3-methyl-3,4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide
  参考文献：
  名称：

  5′-Alkyl-benzothiadiazides: A New Subgroup of AMPA Receptor Modulators with Improved Affinity

  摘要：

  AMPA receptors form a major subdivision of the glutamate receptor family that mediates excitatory synaptic transmission in the brain, Currents through AMPA receptors can be up- or down-regulated by compounds that allosterically modulate receptor kinetics through binding sites distinct from that for glutamate. One of those modulators is the benzothiadiazide IDRA-21 which has been reported to enhance synaptic transmission and be effective in behavioral tests, but typically requires threshold concentrations of at least 100 muM to be active in vitro. In this study, new benzothiadiazides were developed with IDRA-21 as lead compound and examined for their potency in modulating AMPA receptor kinetics. A significant increase in drug affinity was obtained by alkyl substitution at the 5'-position of IDRA-21; substitutions at other positions of the benzothiadiazide core generally did not yield a further gain in affinity and in some cases abolished drug binding. The 5'-ethyl derivative exhibited an EC50 value in the order of 22 muM which represents about a 30-fold gain in affinity over that of IDRA-21. The EC50 value is comparable to that of cyclothiazide, the most potent benzothiadiazide drug, but the effects on AMPA receptors differed substantially between these two compounds in that the 5'-ethyl derivative of IDRA-21 greatly increased the binding affinity for receptor agonists whereas cyclothiazide is known to reduce agonist binding. The structure-activity relationships reported here thus offer to provide new insights how receptor kinetics is linked to particular aspects of receptor-drug interactions. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(01)00405-9

文献信息

• Evaluation of stereo and chemical stability of chiral compounds
  作者：Giuseppe Cannazza、Umberto Battisti、Marina M. Carrozzo、Livio Brasili、Daniela Braghiroli、Carlo Parenti

  DOI：10.1002/chir.20941

  日期：2011.11

  investigate simultaneously the stereo and chemical stability of labile chiral compounds. The single enantiomers of a racemate can be separated on chiral column (first dimension) and each one can be trapped in the achiral column (second dimension) that works as reactor.By filling the achiral column with the appropriate aqueous buffers it is possible to evaluate the stability of the trapped enantiomer toward

  停止流动的二维循环HPLC（sf-BD-rHPLC）配置已用于同时研究不稳定的手性化合物的立体和化学稳定性。外消旋体的单个对映异构体可以在手性色谱柱上分离（第一维），每个都可以被截留在作为反应器的非手性色谱柱（第二维）中。被捕获的对映异构体对水性缓冲液本身的稳定性。可以再循环在手性塔中形成的反应产物（第一维），在该处它们被第二个六个阀口隔开。通过相应的峰面积，计算了在非手性色谱柱中发生的不同过程的反应速率常数。1）在与生物流体相似的条件下评估对映性和水解性。使用经典的间歇动力学方法来计算sf-BD-rHPLC中相同温度和相同溶剂中水解和对映异构的速率常数。获得的结果的良好一致性验证了所开发的新颖程序。此外，离线生成的结果用于确定溶剂对（±）-1外消旋化的影响。手性，2011年。©2011 Wiley‐Liss，Inc.。
• Method for treating sexual dysfunctions
  申请人：The Regents of the University of California

  公开号：US06083947A1

  公开（公告）日：2000-07-04

  This invention is a novel treatment for sexual dysfunctions by administering to a subject exhibiting a sexual dysfunction compounds that upmodulate the AMPA receptor. Methods and compositions for treating sexual dysfunction are provided. Kits containing the compositions in appropriate form for administration are also provided.

  这项发明是通过向表现出性功能障碍的受试者施用上调AMPA受体化合物来治疗性功能障碍的新型方法。提供了治疗性功能障碍的方法和组合物。还提供了包含适合施用的组合物的套件。
• METHOD FOR TREATING SEXUAL DYSFUNCTIONS
  申请人：The Regents of The University of California

  公开号：EP0883403B1

  公开（公告）日：2010-08-25
• 5′-Alkyl-benzothiadiazides: A New Subgroup of AMPA Receptor Modulators with Improved Affinity
  作者：Dean Phillips、Jennifer Sonnenberg、Amy C Arai、Rishi Vaswani、Peter O Krutzik、Thomas Kleisli、Markus Kessler、Richard Granger、Gary Lynch、A Richard Chamberlin

  DOI：10.1016/s0968-0896(01)00405-9

  日期：2002.5

  AMPA receptors form a major subdivision of the glutamate receptor family that mediates excitatory synaptic transmission in the brain, Currents through AMPA receptors can be up- or down-regulated by compounds that allosterically modulate receptor kinetics through binding sites distinct from that for glutamate. One of those modulators is the benzothiadiazide IDRA-21 which has been reported to enhance synaptic transmission and be effective in behavioral tests, but typically requires threshold concentrations of at least 100 muM to be active in vitro. In this study, new benzothiadiazides were developed with IDRA-21 as lead compound and examined for their potency in modulating AMPA receptor kinetics. A significant increase in drug affinity was obtained by alkyl substitution at the 5'-position of IDRA-21; substitutions at other positions of the benzothiadiazide core generally did not yield a further gain in affinity and in some cases abolished drug binding. The 5'-ethyl derivative exhibited an EC50 value in the order of 22 muM which represents about a 30-fold gain in affinity over that of IDRA-21. The EC50 value is comparable to that of cyclothiazide, the most potent benzothiadiazide drug, but the effects on AMPA receptors differed substantially between these two compounds in that the 5'-ethyl derivative of IDRA-21 greatly increased the binding affinity for receptor agonists whereas cyclothiazide is known to reduce agonist binding. The structure-activity relationships reported here thus offer to provide new insights how receptor kinetics is linked to particular aspects of receptor-drug interactions. (C) 2002 Published by Elsevier Science Ltd.
• Regioselective reduction of 3-substituted 2,3-dihydrobenzothiadiazines with borohydrides
  作者：Umberto M. Battisti、Giuseppe Cannazza、Marina M. Carrozzo、Daniela Braghiroli、Carlo Parenti、Francesca Rosato、Luigino Troisi

  DOI：10.1016/j.tetlet.2010.06.081

  日期：2010.8

  A simple and efficient synthetic path for N-1 or N-2 alkyl-substituted 2-aminobenzenesulfonamides was developed based on regioselective reduction with NaBH3CN in different solvents.

  基于在不同溶剂中用NaBH 3 CN进行区域选择性还原，开发了一种N-1或N-2烷基取代的2-氨基苯磺酰胺的简单有效的合成途径。