methyl 4-chloro-2-[[2-(3-nitrophenyl)acetyl]amino]benzoate | 142327-50-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-chloro-2-[[2-(3-nitrophenyl)acetyl]amino]benzoate
• 英文别名: methyl 2-(2-(3-nitrophenyl)acetamido)-4-chlorobenzoate；methyl 4-chloro-2-(2-(3-nitrophenyl)acetamido)benzoate；methyl 4-chloro-2-(3-nitrophenyl)acetamidobenzoate
• CAS: 142327-50-2
• 化学式: C₁₆H₁₃ClN₂O₅
• 分子量: 348.743
• InChiKey: FGLWOKMMRDILGS-UHFFFAOYSA-N

物化性质

• 熔点：
  137-139 °C
• 沸点：
  577.1±50.0 °C(Predicted)
• 密度：
  1.423±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-chloro-2-[[2-(3-nitrophenyl)acetyl]amino]benzoate 在 calcium(II) chloride dihydrate 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 27.0h， 生成 methyl 4-chloro-2-(2-(3-(phenyldiazenyl)phenyl)acetamido)benzoate
  参考文献：
  名称：

  NMDA受体的光开关拮抗剂的开发

  摘要：

  N-甲基-d天冬氨酸受体（NMDAR）对于神经系统过程（例如学习，记忆和突触可塑性）至关重要。这样，调节其功能的小分子在许多神经系统疾病的研究中受到关注。我们已经合成了一个小的光电开关库，可调节NMDAR功能。迄今为止，最有效的光开关是基于甘氨酸结合位点的已知配体，并且显示出显着的亚型选择性。

  DOI：

  10.1016/j.tet.2017.06.056
• 作为产物：
  描述：

  3-硝基苯乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 20.0h， 生成 methyl 4-chloro-2-[[2-(3-nitrophenyl)acetyl]amino]benzoate
  参考文献：
  名称：

  NMDA受体的光开关拮抗剂的开发

  摘要：

  N-甲基-d天冬氨酸受体（NMDAR）对于神经系统过程（例如学习，记忆和突触可塑性）至关重要。这样，调节其功能的小分子在许多神经系统疾病的研究中受到关注。我们已经合成了一个小的光电开关库，可调节NMDAR功能。迄今为止，最有效的光开关是基于甘氨酸结合位点的已知配体，并且显示出显着的亚型选择性。

  DOI：

  10.1016/j.tet.2017.06.056

文献信息

• Hydroxyquinolone derivatives compounds which have pharmaceutical utility
  申请人：Merck Sharpe & Dohme Ltd.

  公开号：US05348962A1

  公开（公告）日：1994-09-20

  This present invention relates to a class of 4-hydroxy-2-(1H)-quinolones which are substituted in the 3-position by an optionally substituted aryl substituent. These compounds are selective non-competitive antagonists of N-methyl-D-aspartate (NMDA) receptors.

  这项发明涉及一类在3位被可选择取代的芳基取代物所取代的4-羟基-2-(1H)-喹啉酮。这些化合物是N-甲基-D-天冬氨酸(NMDA)受体的选择性非竞争性拮抗剂。
• Hydroxyquinolone derivatives
  申请人：Merck, Sharp & Dohme Limited

  公开号：US05559125A1

  公开（公告）日：1996-09-24

  A class of 4-hydroxy-2-(1H)-quinolone derivatives, substituted at the 3-position by an optionally substituted aryl substituent, are selective non-competitive antagonists of NMDA receptors and/or are antagonists of AMPA receptors, and are therefore of utility in the treatment of conditions, such as neurodegenerative disorders, convulsions or schizophrenia, which require the administration of an NMDA and/or AMPA receptor antagonist.

  一类4-羟基-2-(1H)-喹啉衍生物，其在3位被可选择取代的芳基取代基所取代，是NMDA受体的选择性非竞争性拮抗剂和/或AMPA受体的拮抗剂，因此在治疗需要给予NMDA和/或AMPA受体拮抗剂的疾病，如神经退行性疾病、惊厥或精神分裂症等方面具有实用价值。
• 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.
• Development of N-[11C]methylamino 4-hydroxy-2(1H)-quinolone derivatives as PET radioligands for the glycine-binding site of NMDA receptors
  作者：Takeshi Fuchigami、Terushi Haradahira、Noriko Fujimoto、Yumiko Nojiri、Takahiro Mukai、Fumihiko Yamamoto、Takashi Okauchi、Jun Maeda、Kazutoshi Suzuki、Tetsuya Suhara、Hiroshi Yamaguchi、Mikako Ogawa、Yasuhiro Magata、Minoru Maeda

  DOI：10.1016/j.bmc.2009.06.014

  日期：2009.8

  In this study, we synthesized and evaluated several amino 4-hydroxy-2(1H)-quinolone (4HQ) derivatives as new PET radioligand candidates for the glycine site of the NMDA receptors. Among these ligands, we discovered that 7-chloro-4-hydroxy-3-3-(4-methylaminobenzyl) phenyl}-2-(1H)-quinolone (12) and 5-ethyl-7-chloro-4-hydroxy-3-(3-methylaminophenyl)-2(1H)-quinolone (32) have high affinity for the glycine site (K-i values; 11.7 nM for 12 and 11.8 nM for 32). In vitro autoradiography experiments indicated that [C-11]12 and [C-11]32 showed high specific binding in the brain slices, which were strongly inhibited by both glycine agonists and antagonists. In vivo brain uptake of these C-11-labeled 4HQs were examined in normal mice. Cerebellum to blood ratio of accumulation, of both [C-11]12 and [C-11]32 at 30 min were 0.058, which were slightly higher than those of cerebrum to blood ratio (0.043 and 0.042, respectively). These results indicated that [C-11]12 and [C-11]32 have poor blood brain barrier permeability. Although the plasma protein-binding ratio of [C-11]32 was much lower than methoxy analogs (71% vs 94-98%, respectively), [C-11]32 still binds with plasma protein strongly. It is conjectured that still acidic moiety and high affinity with plasma protein of [C-11]32 may prevent in vivo brain uptake. In conclusion, [C-11]12 and [C-11]32 are unsuitable for imaging cerebral NMDA receptors. (C) 2009 Elsevier Ltd. All rights reserved.
• US5348962A
  申请人：——

  公开号：US5348962A

  公开（公告）日：1994-09-20