1-(2-hydroxyphenyl)-3-(naphthalen-2-yl)propane-1,3-dione | 117082-26-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 1-(2-hydroxyphenyl)-3-(naphthalen-2-yl)propane-1,3-dione
• 英文别名: 1-(2-Hydroxyphenyl)-3-(2-naphthalenyl)-1,3-propanedione；1-(2-hydroxyphenyl)-3-naphthalen-2-ylpropane-1,3-dione
• CAS: 117082-26-5
• 化学式: C₁₉H₁₄O₃
• 分子量: 290.318
• InChiKey: BSPRDEISNOGECR-UHFFFAOYSA-N

物化性质

• 熔点：
  141 °C(Solv: acetic acid (64-19-7))
• 沸点：
  509.6±30.0 °C(Predicted)
• 密度：
  1.265±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-hydroxyphenyl)-3-(naphthalen-2-yl)propane-1,3-dione 在 吡啶 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-(4-hydroxybenzyl)-1-(naphthalen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one
  参考文献：
  名称：

  Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure

  摘要：

  Phosphodiesterase-5 (PDE5) inhibitors have been approved for the treatment of erectile dysfunction and pulmonary hypertension, but enthusiasm on discovery of PDE5 inhibitors continues for their potential new applications. Reported here is discovery of a series of new PDE5 inhibitors by structure-based design, molecular docking, chemical synthesis, and enzymatic characterization. The best compound, 3(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one (57), has an IC50 of 17 nM against the PDE5 catalytic domain and good selectivity over other PDE families. The crystal structure of the PDE5 catalytic domain in complex with 57 was determined at 2 angstrom resolution and showed that 57 occupies the same pocket as other PDE5 inhibitors, but has a different binding pattern in detail. On the basis of the binding pattern of 57, a novel scaffold can be proposed as a candidate of PDE inhibitors. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2014.02.013
• 作为产物：
  描述：

  2-萘甲酸 在 吡啶 、 草酰氯 、 potassium hydroxide 作用下， 以 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 1-(2-hydroxyphenyl)-3-(naphthalen-2-yl)propane-1,3-dione
  参考文献：
  名称：

  代谢型谷氨酸受体的正构构调节剂的有效和脑渗透化学系列的发现，结构-活性关系和抗帕金森效应4

  摘要：

  代谢型谷氨酸受体4（mGluR4）是治疗帕金森氏病（PD）的新兴靶标。然而，自发现其治疗潜力以来，没有成功开发出足以在临床上进行测试的配体。在本文中，我们首次报告了围绕药理学工具（-）-PHCCC进行的药物化学研究。这项工作导致了化合物40的鉴定，一种有效的，选择性的mGluR4阳性变构调节剂（PAM），具有良好的水溶性，并在腹膜内给药后在经过验证的PD运动症状的临床前啮齿动物模型中表现出一致的活性：氟哌啶醇在小鼠和大鼠中引起的僵直和6-羟基多巴胺（6-OHDA）病变模型。此外，我们还描述了口服给药后化合物60与化合物40的紧密类似物具有改善的药代动力学特征的鉴定。基于其有利和独特的临床前特性，化合物60（PXT002331，现为foliglurax）被提名为临床开发的候选药物。

  DOI：

  10.1021/acs.jmedchem.7b00991

文献信息

• [EN] NOVEL OXIME DERIVATIVES AND THEIR USE AS ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] NOUVEAUX DÉRIVÉS D'OXIMES ET LEUR UTILISATION COMME MODULATEURS ALLOSTÉRIQUES DE RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE
  申请人：DOMAIN THERAPEUTICS

  公开号：WO2011051478A1

  公开（公告）日：2011-05-05

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGiuR4.

  本发明提供了一般式（I）的新羟肟衍生物，包含它们的药物组合物以及它们用于治疗和/或预防与改变的谷氨酸信号和/或功能有关的疾病，和/或在哺乳动物中改变谷氨酸水平或信号会影响的疾病。本发明进一步提供了一般式（I）的新羟肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。在特定实施例中，本发明的新羟肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向变构调节剂，更具体地说是mGluR4的正向变构调节剂。
• A very simple solvent-free method for the synthesis of 2-arylchromones using KHSO4 as a recyclable catalyst
  作者：María Pérez、Diego Ruiz、Juan Autino、Angel Sathicq、Gustavo Romanelli

  DOI：10.1016/j.crci.2016.02.014

  日期：2016.5

  Résumé An efficient and solvent-free procedure for the synthesis of flavones using KHSO4 as a recyclable catalyst is described. The methodology represents an environmentally friendly process in comprehensive consideration compared with other catalytic systems listed in publications. This method provides a clean, simple, solvent-free reaction and useful alternatives to prepare flavones and chromones. The use of KHSO4 catalyst provides excellent yields, also leading to an easy separation and recovery of the catalysts, which allows both low environmental impact and low cost. Other green advantages of the method are the low formation of wastes and the replacement of corrosive, soluble mineral acids. Supplementary Materials: Supplementary material for this article is supplied as a separate file: mmc1.doc

  摘要 本文描述了一种高效无溶剂的黄酮合成程序，采用KHSO4作为可回收催化剂。这种方法在综合考虑下，与其他文献中列出的催化系统相比，代表了一种环保的过程。该方法提供了一种清洁、简单、无溶剂的反应，并为制备黄酮和色酮提供了有用的替代方案。使用KHSO4催化剂可实现优异的产率，同时便于催化剂的分离和回收，这不仅降低了环境影响，还降低了成本。该方法的其他绿色优势包括废物生成少，以及替代腐蚀性可溶性矿酸。 补充材料： 本文章的补充材料作为单独文件提供：mmc1.doc
• Green and Efficient Synthesis of Flavones and Chromones Using Heteropolyacids as Catalyst in Glycerol
  作者：Maria Belen Colombo Migliorero、Valeria Palermo、Edwin Alexis Alarcon Durango、Aída Luz Villa Holguin、Patricia Graciela Vazquez、Angel Gabriel Sathicq、Gustavo Pablo Romanelli

  DOI：10.2174/1570178615666180509150014

  日期：2018.8.8

  Fil: Colombo Migliorero, Maria Belen. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - La Plata. Centro de Investigacion y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigacion y Desarrollo en Ciencias Aplicadas; Argentina

  菲尔：科伦坡米廖雷罗，玛丽亚贝伦。Consejo Nacional de Investigaciones Cientificas y Tecnicas。Centro Cientifico Tecnologico Conicet - 拉普拉塔。Centro de Investigacion y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco"。拉普拉塔国立大学。Facultad de Ciencias Exactas。Centro de Investigacion y Desarrollo en Ciencias Aplicadas；阿根廷
• Novel Oxime Derivatives and Their Use As Allosteric Modulators of Metabotropic Glutamate Receptors
  申请人：Schann Stephan

  公开号：US20120277212A1

  公开（公告）日：2012-11-01

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGluR4.

  本发明提供了一般式（I）的新的肟衍生物，以及包含它们的制药组合物，以及它们用于治疗和/或预防与改变谷氨酸信号和/或功能相关的疾病和/或与哺乳动物中谷氨酸水平或信号改变有关的疾病的用途。本发明还提供了一般式（I）的新的肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。在特定实施例中，本发明的新的肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向异构调节剂，更具体地说是mGluR4的正向异构调节剂。
• 10.1016/j.tet.2024.134087
  作者：Chen, Yongdan、Deng, Tongtong、Zhu, Shuwei、Yin, Fumeng、Zhu, Hongjun

  DOI：10.1016/j.tet.2024.134087

  日期：——

  divergent synthesis of chromones and chromanones from a common substrate via reductive coupling cyclization by switching hydrosilanes has been developed. Results of mechanistic studies revealed that under PhMeSiH conditions, the reaction initially undergone cyclization to form chromones , which can subsequently be reduced to yield chromanones . When the hydrosilane was switched to EtSiH, the reaction route

  开发了一种使用AgOTf/[Si]H通过切换氢硅烷的还原偶联环化从共同底物高效且发散地合成色酮和色满酮的方法。机理研究结果表明，在PhMeSiH条件下，反应最初发生环化形成色酮，随后可被还原生成色酮。当氢硅烷换成EtSiH时，反应路线在色酮处停止，CC不能进一步还原。这种新颖、温和的方案具有广泛的官能团兼容性、高产品多样性以及在构建生物相关色酮或色满酮衍生物方面的实用性。