7-乙基-2H-1,2,4-苯并噻二嗪-3(4H)-酮1,1-二氧化物 | 616224-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 中文名称: 7-乙基-2H-1,2,4-苯并噻二嗪-3(4H)-酮1,1-二氧化物
• 英文名称: 7-ethyl-2H,4H-benzo[e]1,2,4-thiadiazine-1,1,3-trione
• 英文别名: 2H-1,2,4-Benzothiadiazin-3(4H)-one,7-ethyl-,1,1-dioxide(9CI)；7-ethyl-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-one
• CAS: 616224-75-0
• 化学式: C₉H₁₀N₂O₃S
• 分子量: 226.256
• InChiKey: IOKCVOREBFCTIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-乙基-2H-1,2,4-苯并噻二嗪-3(4H)-酮1,1-二氧化物 在 硫酸 作用下， 以 水 为溶剂， 反应 2.0h， 生成 2-氨基-5-乙基苯磺酰胺
  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
• 作为产物：
  描述：

  4-乙基苯胺 在 三氯化铝 作用下， 以 various solvent(s) 为溶剂， 反应 2.0h， 生成 7-乙基-2H-1,2,4-苯并噻二嗪-3(4H)-酮1,1-二氧化物
  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

• Piperidine derivatives having ccr3 antagonism
  申请人：Matsumoto Yoshiyuki

  公开号：US20070032525A1

  公开（公告）日：2007-02-08

  The invention provides low molecular compounds having activity which inhibits binding of CCR3 ligands to CCR3 on target cells, i.e. CCR3 antagonists. The invention also provides compounds represented by formula (I) below, pharmaceutically acceptable acid adducts thereof, or pharmaceutically acceptable C 1 -C 6 alkyl adducts thereof, as well as pharmaceutical compositions comprising them as effective ingredients, which are useful for treatment or prevention of diseases associated with CCR3, such as asthma and allergic rhinitis.

  本发明提供了具有抑制CCR3配体结合到靶细胞CCR3的活性的低分子化合物，即CCR3拮抗剂。本发明还提供了由下式（I）表示的化合物，其药学上可接受的酸加合物或药学上可接受的C1-C6烷基加合物，以及包含它们作为有效成分的制药组合物，用于治疗或预防与CCR3相关的疾病，例如哮喘和过敏性鼻炎。
• PIPERIDINE DERIVATIVES HAVING CCR3 ANTAGONISM
  申请人：TEIJIN LIMITED

  公开号：EP1502916A1

  公开（公告）日：2005-02-02

  The invention provides low molecular compounds having activity which inhibits binding of CCR3 ligands to CCR3 on target cells, i.e. CCR3 antagonists. The invention also provides compounds represented by formula (I) below, pharmaceutically acceptable acid adducts thereof, or pharmaceutically acceptable C1-C6 alkyl adducts thereof, as well as pharmaceutical compositions comprising them as effective ingredients, which are useful for treatment or prevention of diseases associated with CCR3, such as asthma and allergic rhinitis.

  本发明提供了具有抑制 CCR3 配体与靶细胞上 CCR3 结合活性的低分子化合物，即 CCR3 拮抗剂。本发明还提供了下式(I)代表的化合物、其药学上可接受的酸加合物或其药学上可接受的C1-C6烷基加合物，以及包含它们作为有效成分的药物组合物，这些化合物可用于治疗或预防与CCR3相关的疾病，如哮喘和过敏性鼻炎。
• US7517875B2
  申请人：——

  公开号：US7517875B2

  公开（公告）日：2009-04-14
• 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.