3-(2-(4-(2,3-dimethoxybenzoyl)-piperidin-1-yl)-ethyl)-2-thioxo-2,3-dihydro-1H-quinazolin-4-one | 1253641-22-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(2-(4-(2,3-dimethoxybenzoyl)-piperidin-1-yl)-ethyl)-2-thioxo-2,3-dihydro-1H-quinazolin-4-one
• 英文别名: 3-(2-{4-[(2,3-Dimethoxyphenyl)carbonyl]piperidin-1-yl}ethyl)-2-sulfanylidene-1,2,3,4-tetrahydroquinazolin-4-one, 4a；3-[2-[4-(2,3-dimethoxybenzoyl)piperidin-1-yl]ethyl]-2-sulfanylidene-1H-quinazolin-4-one
• CAS: 1253641-22-3
• 化学式: C₂₄H₂₇N₃O₄S
• 分子量: 453.562
• InChiKey: SLXMMZDZUNMMSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (2,3-二甲氧基苯基)(哌啶-4-基)甲酮 在 potassium carbonate 、 三氟乙酸 、 potassium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-(2-(4-(2,3-dimethoxybenzoyl)-piperidin-1-yl)-ethyl)-2-thioxo-2,3-dihydro-1H-quinazolin-4-one
  参考文献：
  名称：

  Research Letter: Structural Combination of Established 5-HT2A Receptor Ligands: New Aspects of the Binding Mode

  摘要：

  MH.MZ, MDL 100907, and altanserin are structurally similar 4‐benzoyl‐piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high‐affinity and selective 5‐HT2A antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4‐benzoyl‐piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [3H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5‐HT2A receptor (Ki = 57 nm). The remarkably reduced affinity of other compounds (4a), (4b), and (4c) (Ki = 411, 360 and 356 nm respectively) indicates that MH.MZ can only bind to the 5‐HT2A receptor with the p‐fluorophenylethyl residue in a sterically restricted hydrophobic binding pocket.

  DOI：

  10.1111/j.1747-0285.2010.01011.x

文献信息

• Research Letter: Structural Combination of Established 5-HT2A Receptor Ligands: New Aspects of the Binding Mode
  作者：Vasko Kramer、Matthias M. Herth、Martin A. Santini、Mikael Palner、Gitte M. Knudsen、Frank Rösch

  DOI：10.1111/j.1747-0285.2010.01011.x

  日期：2010.10

  MH.MZ, MDL 100907, and altanserin are structurally similar 4‐benzoyl‐piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high‐affinity and selective 5‐HT2A antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4‐benzoyl‐piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [3H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5‐HT2A receptor (Ki = 57 nm). The remarkably reduced affinity of other compounds (4a), (4b), and (4c) (Ki = 411, 360 and 356 nm respectively) indicates that MH.MZ can only bind to the 5‐HT2A receptor with the p‐fluorophenylethyl residue in a sterically restricted hydrophobic binding pocket.