6,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid | 148520-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid
• 英文别名: 6,7-dimethoxy-4-oxochromene-2-carboxylic acid
• CAS: 148520-13-2
• 化学式: C₁₂H₁₀O₆
• 分子量: 250.208
• InChiKey: DUDLETOLCPARBW-UHFFFAOYSA-N

物化性质

• 熔点：
  303 °C (decomp)
• 沸点：
  434.4±45.0 °C(Predicted)
• 密度：
  1.426±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid 在 盐酸 、 三溴化硼 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 N-{10-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-6,7-dihydroxy-4-oxo-4H-chromene-2-carboxamide hydrochloride
  参考文献：
  名称：

  New Tacrine–4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

  摘要：

  By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a new family of tacrine-4-oxo-4H-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4H-chromene was chosen for its radical capture and beta-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine-4-oxo-4H-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- N-{10-[(1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-4 H-chromene-2-carboxamide (19) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties.

  DOI：

  10.1021/jm201460y
• 作为产物：
  描述：

  3,4-二甲氧基苯酚 在 硫酸 、 三乙胺 、 乙酰氯 、 sodium hydroxide 作用下， 以 乙醚 为溶剂， 反应 1.0h， 生成 6,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid
  参考文献：
  名称：

  Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease

  摘要：

  In this work we describe neurogenic and neuroprotective donepezil-flavonoid hybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (sigma R-1) and inhibition of key enzymes in Alzheimer's disease (AD), such as acetylcholinesterase (AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, new compounds scavenge free radical species, are predicted to be brain-permeable, and protect neuronal cells against mitochondrial oxidative stress. N-(2-(1-Benzylpiperidin-4-yl)ethyl)-6,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide (18) is highlighted due to its interesting biological profile in sigma R-1, AChE, 5-LOX, MAO-A and MAO-B. In phenotypic assays, it protects a neuronal cell line against mitochondrial oxidative stress and promotes maturation of neural stem cells into a neuronal phenotype, which could contribute to the reparation of neuronal tissues. Molecular modelling studies of 18 in AChE, 5-LOX and sigma R-1 revealed the main interactions with these proteins, which will be further exploited in the optimization of new, more efficient DFHs. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.07.026

文献信息

• [EN] SUBSTITUTED CYCLOLAKYLS AS MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] CYCLOLALKYLES SUBSTITUÉS EN TANT QUE MODULATEURS DE LA VOIE DE STRESS INTÉGRÉE
  申请人：CALICO LIFE SCIENCES LLC

  公开号：WO2020223536A1

  公开（公告）日：2020-11-05

  Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.

  本文提供了用于调节综合应激反应（ISR）并治疗相关疾病、疾病和症状的化合物、组合物和方法。
• [EN] SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS<br/>[FR] DERIVES DE PIPERIDINE ET DE PIPERAZINE SUBSTITUES UTILISES EN TANT QUE MODULATEURS DU RECEPTEUR DE LA MELANOCORTINE-4
  申请人：MYOCONTRACT LTD

  公开号：WO2004083208A1

  公开（公告）日：2004-09-30

  The present invention relates to novel substituted piperidine and piperazine derivatives as melanocortin-4 receptor (MC-4R) modulators. MC-4R agonists of the invention can be used for the treatment of disorders and diseases such as obesity, diabetes and sexual dysfunction, whereas the MC-4R antagonists are useful for the treatment of disorders and diseases such as cancer cachexia, muscle wasting, anorexia, anxiety and depression. All diseases and disorders, where the regulation of the MC-4R is involved, can be treated with the compounds of the invention.

  本发明涉及一种新型的替代哌啶和哌嗪衍生物，作为黑色素皮质素-4受体（MC-4R）调节剂。本发明的MC-4R激动剂可用于治疗肥胖、糖尿病和性功能障碍等疾病，而MC-4R拮抗剂可用于治疗癌症恶病质、肌肉消耗、厌食症、焦虑和抑郁等疾病。所有涉及MC-4R调节的疾病和障碍均可使用本发明的化合物治疗。
• New flavonoid – <i>N</i>,<i>N</i>-dibenzyl(<i>N</i>-methyl)amine hybrids: Multi-target-directed agents for Alzheimer´s disease endowed with neurogenic properties
  作者：Martín Estrada-Valencia、Clara Herrera-Arozamena、Concepción Pérez、Dolores Viña、José A. Morales-García、Ana Pérez-Castillo、Eva Ramos、Alejandro Romero、Erik Laurini、Sabrina Pricl、María Isabel Rodríguez-Franco

  DOI：10.1080/14756366.2019.1581184

  日期：2019.1.1

  pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privileged scaffolds with well-known activities in ND-targets, the flavonoid and the N,N-dibenzyl(N-methyl)amine (DBMA) fragments, new CNS-permeable flavonoid - DBMA hybrids (1-13) were obtained. They were

  多靶标定向配体（MTDLs）的设计是获得有效的复杂病理学药物的有效方法。结合神经修复特性并阻断神经毒性级联反应第一步的MTDL可能是治疗神经退行性疾病（ND）的长期以来一直希望的补救措施。通过将两个具有众所周知的ND目标活性的特权支架，类黄酮和N，N-二苄基（N-甲基）胺（DBMA）片段连接起来，获得了新的CNS渗透性类黄酮-DBMA杂种（1-13）。 。他们在一系列涉及阿尔茨海默氏病（AD）和其他ND的靶标中进行了生物学评估，这些靶标分别是人胆碱酯酶（hAChE / hBuChE），β-分泌酶（hBACE-1），单胺氧化酶（hMAO-A / B），脂氧合酶5（hLOX-5）和sigma受体（σ1R/σ2R）。经过漏斗式筛选后，6 7-二甲氧基色酮-DBMA（6）因其具有神经源性和在hAChE，hLOX-5，hBACE-1和σ1R中具有有趣的MTD谱而突出显示。分子动力学模拟显示杂种6最相
• [EN] SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS<br/>[FR] DERIVES A SUBSTITUTION PIPERIDINE ET PIPERAZINE AGISSANT COMME MODULATEURS DU RECEPTEUR DE LA MELANOCORTINE 4
  申请人：MYOCONTRACT LTD

  公开号：WO2004083199A1

  公开（公告）日：2004-09-30

  The present invention relates to novel substituted piperidine and piperazine derivatives as melanocortin-4 receptor (MC-4R) modulators. MC-4R agonists of the invention can be used for the treatment of disorders and diseases such as obesity, diabetes, and sexual dysfunction, whereas the MC-4R antagonists are useful for the treatment of disorders and diseases such as cancer cachexia, muscle wasting, anorexia, anxiety and depression. All diseases and disorders where the regulation of the MC-4R is involved can be treated with the compounds of the invention.

  本发明涉及一种新型的取代哌啶和哌嗪衍生物，作为黑色素皮质素-4受体（MC-4R）调节剂。本发明中的MC-4R激动剂可用于治疗肥胖症、糖尿病和性功能障碍等疾病和疾病，而MC-4R拮抗剂则可用于治疗癌症恶病质、肌肉萎缩、厌食、焦虑和抑郁等疾病和疾病。所有涉及MC-4R调节的疾病和疾病都可以用本发明中的化合物进行治疗。
• Substituted cyclohexyl and piperidinyl derivates as melanocortin-4 receptor modulators
  申请人：Soeberdt Michael

  公开号：US20070155783A1

  公开（公告）日：2007-07-05

  The present invention relates to novel substituted cyclohexyl and piperidinyl derivatives as melanocortin-4. receptor (MC-4R) modulators. MC-4R agonists of the invention can be used for the treatment of disorders and diseases such as obesity, diabetes and sexual dysfunction, whereas the MC-4R antagonists are useful for the treatment of disorders and diseases such as cancer cachexia, muscle wasting, anorexia, anxiety and depression. All diseases and disorders where the regulation of the MC-4R is involved can be treated with the compounds of the invention.

  本发明涉及一种新型的取代环己基和哌啶基衍生物，作为黑色素皮质素-4受体（MC-4R）调节剂。本发明中的MC-4R激动剂可用于治疗肥胖症、糖尿病和性功能障碍等疾病和疾病，而MC-4R拮抗剂则可用于治疗癌症消瘦、肌肉消耗、厌食、焦虑和抑郁等疾病和疾病。所有涉及MC-4R调节的疾病和疾病均可使用本发明中的化合物进行治疗。