2-(7-Fluoro-3,5-dimethyl-1,1-dioxo-3,4-dihydro-1H-1λ6-benzo[1,2,4]thiadiazin-2-yl)-ethanol | 204844-06-4

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 2-(7-Fluoro-3,5-dimethyl-1,1-dioxo-3,4-dihydro-1H-1λ6-benzo[1,2,4]thiadiazin-2-yl)-ethanol
• CAS: 204844-06-4
• 化学式: C₁₁H₁₅FN₂O₃S
• 分子量: 274.316
• InChiKey: UYPBOBNDXAHSTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.89
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  69.64
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(7-Fluoro-3,5-dimethyl-1,1-dioxo-3,4-dihydro-1H-1λ6-benzo[1,2,4]thiadiazin-2-yl)-ethanol 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以58%的产率得到
  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-氟-2-甲基苯胺 在 三氯化铝 、 3 A molecular sieve 、 硫酸 、 camphor-10-sulfonic acid 、 仲丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 水 、 乙腈 为溶剂， 反应 25.0h， 生成 2-(7-Fluoro-3,5-dimethyl-1,1-dioxo-3,4-dihydro-1H-1λ6-benzo[1,2,4]thiadiazin-2-yl)-ethanol
  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