4-[6-甲氧基-2-[(1E)-2-(3-硝基苯基)乙烯基]-4-氧代-3(4H)-喹唑啉基]苯甲酸 | 1237744-13-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-[6-甲氧基-2-[(1E)-2-(3-硝基苯基)乙烯基]-4-氧代-3(4H)-喹唑啉基]苯甲酸
• 中文别名: 4-[6-甲氧基-2-[(1e)-2-(3-硝基苯基)乙烯]-4-氧代-3(4h)-喹唑啉]-苯甲酸
• 英文名称: QNZ-46
• 英文别名: 4-[6-methoxy-2-[(1E)-2-(3-nitrophenyl)ethenyl]-4-oxo-3(4H)-quinazolinyl]benzoic acid；4-[6-Methoxy-2-[(1E)-2-(3-nitrophenyl)ethenyl]-4-oxo-3(4H)-quinazolinyl]-benzoic Acid；4-[6-methoxy-2-[(E)-2-(3-nitrophenyl)ethenyl]-4-oxoquinazolin-3-yl]benzoic acid
• CAS: 1237744-13-6
• 化学式: C₂₄H₁₇N₃O₆
• 分子量: 443.415
• InChiKey: GNLVJIICVWDSNI-LFYBBSHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[6-甲氧基-2-[(1E)-2-(3-硝基苯基)乙烯基]-4-氧代-3(4H)-喹唑啉基]苯甲酸 在 tris(bipyridine)ruthenium(II) dichloride hexahydrate 作用下， 以 氘代二甲亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 4-[6-methoxy-2-[(Z)-2-(3-nitrophenyl)ethenyl]-4-oxoquinazolin-3-yl]benzoic acid
  参考文献：
  名称：

  通过光催化异构化对治疗剂进行光化学控制

  摘要：

  使用 Ru(bpy) 3 Cl 2光催化剂，可以实现一系列基于烯烃核心的药物的快速反式到顺式异构化。其中包括康布他汀 A-4 (CA-4)，一种肿瘤学临床候选药物和白藜芦醇衍生物，允许它们在纤维素活化中具有选择性。这为未经修饰的药剂的快速原位激活提供了一个新平台。

  DOI：

  10.1002/anie.202203390
• 作为产物：
  描述：

  4-(6-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)benzoic acid 、 间硝基苯甲醛 在 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以55%的产率得到4-[6-甲氧基-2-[(1E)-2-(3-硝基苯基)乙烯基]-4-氧代-3(4H)-喹唑啉基]苯甲酸
  参考文献：
  名称：

  Quinazolin-4-one Derivatives: A Novel Class of Noncompetitive NR2C/D Subunit-Selective N-Methyl-d-aspartate Receptor Antagonists

  摘要：

  We describe a new class of subunit-selective antagonists of N-methyl D-aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives is noncompetitive and voltage-independent, suggesting that this family of compounds does not exert action on the agonist binding site of the receptor or block the channel pore. The compounds described here resemble CP-465,022 ((S)-3-(2-chlorophenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl]-6-fluoro-3H-quinazolin-4-one), a noncompetitive antagonist of AMPA-selective glutamate receptors. However, modification of ring substituents resulted in analogues with greater than 100-fold selectivity for recombinant NMDA receptors over AMPA and kainate receptors. Furthermore, within this series of compounds, analogues were identified with 50-fold selectivity for recombinant NR2C/D-containing receptors over NR2A/B containing receptors. These compounds represent a new class of noncompetitive subunit-selective NMDA receptor antagonists.

  DOI：

  10.1021/jm100027p

文献信息

• Subunit Selective NMDA Receptor Antagonists For The Treatment Of Neurological Conditions
  申请人：Traynelis Stephen F.

  公开号：US20110319416A1

  公开（公告）日：2011-12-29

  Provided are compounds, pharmaceutical compositions and methods of treating or preventing disorders associated with NMDA receptor activity, including schizophrenia, Parkinson's disease, cognitive disorders, depression, neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds of the general Formulas A-E, and pharmaceutically acceptable salts, esters, prodrugs or derivatives thereof are disclosed.
• [EN] SUBUNIT SELECTIVE NMDA RECEPTOR ANTAGONISTS FOR THE TREATMENT OF NEUROLOGICAL CONDITIONS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR NMDA, SÉLECTIFS POUR DES SOUS-UNITÉS, ET DESTINÉS AU TRAITEMENT D'ÉTATS NEUROLOGIQUES
  申请人：UNIV EMORY

  公开号：WO2010088408A2

  公开（公告）日：2010-08-05

  Provided are compounds, pharmaceutical compositions and methods of treating or preventing disorders associated with NMDA receptor activity, including schizophrenia, Parkinson's disease, cognitive disorders, depression, neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds of the general Formulas A-E, and pharmaceutically acceptable salts, esters, prodrugs or derivatives thereof are disclosed.
• [EN] A HIGH-THROUGHPUT ASSAY METHOD FOR IDENTIFYING ALLOSTERIC NMDA RECEPTOR MODULATORS<br/>[FR] MÉTHODE DE DOSAGE À HAUT DÉBIT POUR IDENTIFIER DES MODULATEURS DU RÉCEPTEUR DE NMDA ALLOSTÉRIQUES
  申请人：NOVARTIS AG

  公开号：WO2017109709A2

  公开（公告）日：2017-06-29

  A novel, high-throughput assay and methods to study N-methyl-D-aspartate receptors (NMDARs). The method allows for rapid comparisons of different subunits, the ability to measure effects of agonists for both the glycine binding site and the glutamate binding 5 site. The methods leverage the use of weak glycine and glutamate sites binding antagonists rather than to ketamine or MK-801 to mitigate against cellular toxicity and to retain the ligand binding site in a ligand-free state. The method can use baculovirus vectors to introduce titratable amounts of different receptor subunits. The assay replicates the pharmacology of NMDARs in response to known antagonists and allosteric 10 modulators, as well as sensitivity to magnesium.
• [EN] NEUROPROTECTIVE COMPOSITION<br/>[FR] COMPOSITION NEUROPROTECTRICE
  申请人：UNIV PLYMOUTH

  公开号：WO2020069934A1

  公开（公告）日：2020-04-09

  Described is a composition for protecting against demyelination and other forms of myelin injury, comprising a combination of an NDMA-type glutamate receptor antagonist and a non-NMDA-type glutamate receptor antagonist.
• Quinazolin-4-one Derivatives: A Novel Class of Noncompetitive NR2C/D Subunit-Selective <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptor Antagonists
  作者：Cara A. Mosley、Timothy M. Acker、Kasper B. Hansen、Praseeda Mullasseril、Karen T. Andersen、Phuong Le、Kimberly M. Vellano、Hans Bräuner-Osborne、Dennis C. Liotta、Stephen F. Traynelis

  DOI：10.1021/jm100027p

  日期：2010.8.12

  We describe a new class of subunit-selective antagonists of N-methyl D-aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives is noncompetitive and voltage-independent, suggesting that this family of compounds does not exert action on the agonist binding site of the receptor or block the channel pore. The compounds described here resemble CP-465,022 ((S)-3-(2-chlorophenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl]-6-fluoro-3H-quinazolin-4-one), a noncompetitive antagonist of AMPA-selective glutamate receptors. However, modification of ring substituents resulted in analogues with greater than 100-fold selectivity for recombinant NMDA receptors over AMPA and kainate receptors. Furthermore, within this series of compounds, analogues were identified with 50-fold selectivity for recombinant NR2C/D-containing receptors over NR2A/B containing receptors. These compounds represent a new class of noncompetitive subunit-selective NMDA receptor antagonists.