1-(4-hydroxy-6-methyl-2-thioxo-1,2-dihydroquinolin-3-yl)hexan-1-one | 1357448-25-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-(4-hydroxy-6-methyl-2-thioxo-1,2-dihydroquinolin-3-yl)hexan-1-one
• CAS: 1357448-25-9
• 化学式: C₁₆H₁₉NO₂S
• 分子量: 289.398
• InChiKey: PLNBOMGPIAAIPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.67
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  53.09
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(4-hydroxy-6-methyl-2-thioxo-1,2-dihydroquinolin-3-yl)hexan-1-one 在 lithium hydroxide 、 hydroxylamine-O-sulfonic acid 作用下， 以 甲醇 为溶剂， 反应 30.0h， 以93%的产率得到6-methyl-3-pentylisothiazolo[5,4-b]quinolin-4(9H)-one
  参考文献：
  名称：

  3-Alkyl- and 3-amido-isothiazoloquinolin-4-ones as ligands for the benzodiazepine site of GABAA receptors

  摘要：

  Based on a pharmacophore model of the benzodiazepine binding site of the GABA(A) receptors, developed with synthetic flavones and potent 3-carbonylquinolin-4-ones, 3-alkyl- and 3-amido-6-methylisothiazoloquinolin-4-ones were designed, prepared and assayed. The suggestion that the interaction between the hydrogen bond donor site H1 with the 3-carbonyl oxygen in 3-carbonylquinolin-4-ones can be replaced by an interaction between H1 and N-2 in the isothiazoloquinolin-4-ones, was confirmed. As with the 3-carbonylquinolin-4-ones, the length of the chain in position 3 is critical for an efficient interaction with the lipophilic pockets of the pharmacophore model. The most potent 3-alkyl derivative, 3-pentyl-6-methylisothiazoloquinolin-4-one, has an affinity (K-i value) for the benzodiazepine binding site of the GABA(A) receptors of 13 nM. However, by replacing the 3-pentyl with a 3-butyramido group an even more potent compound was obtained, with a K-i value of 2.8 nM, indicating that the amide function facilitates additional interactions with the binding site. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2011.10.001
• 作为产物：
  描述：

  2-庚酮 在 sodium methylate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 7.0h， 生成 1-(4-hydroxy-6-methyl-2-thioxo-1,2-dihydroquinolin-3-yl)hexan-1-one
  参考文献：
  名称：

  3-Alkyl- and 3-amido-isothiazoloquinolin-4-ones as ligands for the benzodiazepine site of GABAA receptors

  摘要：

  Based on a pharmacophore model of the benzodiazepine binding site of the GABA(A) receptors, developed with synthetic flavones and potent 3-carbonylquinolin-4-ones, 3-alkyl- and 3-amido-6-methylisothiazoloquinolin-4-ones were designed, prepared and assayed. The suggestion that the interaction between the hydrogen bond donor site H1 with the 3-carbonyl oxygen in 3-carbonylquinolin-4-ones can be replaced by an interaction between H1 and N-2 in the isothiazoloquinolin-4-ones, was confirmed. As with the 3-carbonylquinolin-4-ones, the length of the chain in position 3 is critical for an efficient interaction with the lipophilic pockets of the pharmacophore model. The most potent 3-alkyl derivative, 3-pentyl-6-methylisothiazoloquinolin-4-one, has an affinity (K-i value) for the benzodiazepine binding site of the GABA(A) receptors of 13 nM. However, by replacing the 3-pentyl with a 3-butyramido group an even more potent compound was obtained, with a K-i value of 2.8 nM, indicating that the amide function facilitates additional interactions with the binding site. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2011.10.001