3-(3-aminophenyl)-7-chloro-4-hydroxyquinolin-2(1H)-one | 223736-86-5

• 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: 3-(3-aminophenyl)-7-chloro-4-hydroxyquinolin-2(1H)-one
• 英文别名: 3-(3-aminophenyl)-7-chloro-4-hydroxy-1H-quinolin-2-one
• CAS: 223736-86-5
• 化学式: C₁₅H₁₁ClN₂O₂
• 分子量: 286.718
• InChiKey: KVVDKAVNZUUXRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  乙烯磺酰氟 、 3-(3-aminophenyl)-7-chloro-4-hydroxyquinolin-2(1H)-one 在 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以69%的产率得到2-[3-(7-Chloro-4-hydroxy-2-oxo-1,2-dihydro-quinolin-3-yl)-phenylamino]-ethanesulfonyl fluoride
  参考文献：
  名称：

  Evaluation and Biological Properties of Reactive Ligands for the Mapping of the Glycine Site on the N-Methyl-d-aspartate (NMDA) Receptor

  摘要：

  The glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, given its potential as pharmacological target, has been thoroughly studied by structure-activity relationships, which has made possible its description in terms of spatial limits and interactions of various types. A structural model, based on mutational analysis and sequence alignements, has been proposed. Yet, the amino acid residues responsible for the interactions with the ligand have not been unambiguously characterized. To evidence nucleophilic pocket-lining residues, we have designed and synthesized reactive glycine-site ligands derived from 3-substituted 4-hydroxy-quinolin-2(1H)-ones by introducing various electrophilic groups at different positions of the molecule. These ligands were found to have high affinity at the glycine site and to be functional antagonists by inhibiting glycine/glutamate-induced currents in transfected oocytes. The correlation between their potency and their substitution pattern was strictly consistent with previously established structure-activity relationships. Most ligands displayed intrinsic reactivity toward cysteine, but none inactivated wild-type receptors. This is consistent with the model since it indicates the absence of exposed cysteine in the glycine-binding site. A strategy of cysteine incorporation by point mutations at selected polypeptide positions will create unambiguously localized targets for our reactive probes.

  DOI：

  10.1021/jm9910730
• 作为产物：
  描述：

  7-chloro-4-hydroxy-3-(3-nitrophenyl)quinolin-2(1H)-one 在 盐酸 、 titanium(III) chloride 作用下， 以 四氢呋喃 为溶剂， 以60%的产率得到3-(3-aminophenyl)-7-chloro-4-hydroxyquinolin-2(1H)-one
  参考文献：
  名称：

  Evaluation and Biological Properties of Reactive Ligands for the Mapping of the Glycine Site on the N-Methyl-d-aspartate (NMDA) Receptor

  摘要：

  The glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, given its potential as pharmacological target, has been thoroughly studied by structure-activity relationships, which has made possible its description in terms of spatial limits and interactions of various types. A structural model, based on mutational analysis and sequence alignements, has been proposed. Yet, the amino acid residues responsible for the interactions with the ligand have not been unambiguously characterized. To evidence nucleophilic pocket-lining residues, we have designed and synthesized reactive glycine-site ligands derived from 3-substituted 4-hydroxy-quinolin-2(1H)-ones by introducing various electrophilic groups at different positions of the molecule. These ligands were found to have high affinity at the glycine site and to be functional antagonists by inhibiting glycine/glutamate-induced currents in transfected oocytes. The correlation between their potency and their substitution pattern was strictly consistent with previously established structure-activity relationships. Most ligands displayed intrinsic reactivity toward cysteine, but none inactivated wild-type receptors. This is consistent with the model since it indicates the absence of exposed cysteine in the glycine-binding site. A strategy of cysteine incorporation by point mutations at selected polypeptide positions will create unambiguously localized targets for our reactive probes.

  DOI：

  10.1021/jm9910730

文献信息

• Evaluation and Biological Properties of Reactive Ligands for the Mapping of the Glycine Site on the <i>N</i>-Methyl-<scp>d</scp>-aspartate (NMDA) Receptor
  作者：Annett Kreimeyer、Bodo Laube、Mike Sturgess、Maurice Goeldner、Bernard Foucaud

  DOI：10.1021/jm9910730

  日期：1999.10.1

  The glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, given its potential as pharmacological target, has been thoroughly studied by structure-activity relationships, which has made possible its description in terms of spatial limits and interactions of various types. A structural model, based on mutational analysis and sequence alignements, has been proposed. Yet, the amino acid residues responsible for the interactions with the ligand have not been unambiguously characterized. To evidence nucleophilic pocket-lining residues, we have designed and synthesized reactive glycine-site ligands derived from 3-substituted 4-hydroxy-quinolin-2(1H)-ones by introducing various electrophilic groups at different positions of the molecule. These ligands were found to have high affinity at the glycine site and to be functional antagonists by inhibiting glycine/glutamate-induced currents in transfected oocytes. The correlation between their potency and their substitution pattern was strictly consistent with previously established structure-activity relationships. Most ligands displayed intrinsic reactivity toward cysteine, but none inactivated wild-type receptors. This is consistent with the model since it indicates the absence of exposed cysteine in the glycine-binding site. A strategy of cysteine incorporation by point mutations at selected polypeptide positions will create unambiguously localized targets for our reactive probes.