3-(m-methoxyphenyl)-6-methylcoumarin | 1190439-37-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 3-(m-methoxyphenyl)-6-methylcoumarin
• 英文别名: 3-(3-methoxyphenyl)-6-methylcoumarin；3-(3-methoxyphenyl)-6-methyl-2H-chromen-2-one；3-(3-methoxyphenyl)-6-methylchromen-2-one
• CAS: 1190439-37-2
• 化学式: C₁₇H₁₄O₃
• 分子量: 266.296
• InChiKey: FXKIDMXANLWDBM-UHFFFAOYSA-N

物化性质

• 熔点：
  84-85 °C
• 沸点：
  455.5±45.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(m-methoxyphenyl)-6-methylcoumarin 在 氢碘酸 、 乙酸酐 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 19.0h， 生成 6-methyl-3-[3-(2-oxopropoxy)phenyl]coumarin
  参考文献：
  名称：

  Synthesis and Study of a Series of 3-Arylcoumarins as Potent and Selective Monoamine Oxidase B Inhibitors

  摘要：

  New series of 6-substituted-3-arylcoumarins displaying several alkyl, hydroxyl, halogen, and alkoxy groups in the two benzene rings have been designed, synthesized, and evaluated in vitro as human monoamine cuddase A and B (hMAO-A and hMAO-B) inhibitors. Most of the studied compounds showed a high affinity and selectivity to the hMAO-B isoenzyme, with IC50 values on nanomolar and picomolar range. Ten of the 22 described compounds displayed higher MAO-B inhibitory activity and selectivity than selegiline. Coumarin 7 is the most active compound of this series, being 64 times more active than selegiline and also showing the highest hMAO-B specificity. In addition, docking experiments were carried out on hMAO-A and h-MAO-B structures. This study provided new information about the enzyme inhibitor interaction and the potential therapeutic application of this 3-arylcoumarin scaffold.

  DOI：

  10.1021/jm200716y
• 作为产物：
  描述：

  3-乙炔基苯甲醚 、 (E)-N'-(2-hydroxy-5-methylbenzylidene)-4-methylbenzenesulfonohydrazide 在 potassium tert-butylate 、 氧气 、 copper(l) chloride 作用下， 以 乙腈 为溶剂， 反应 14.0h， 以1.09 g的产率得到3-(m-methoxyphenyl)-6-methylcoumarin
  参考文献：
  名称：

  N-甲苯磺酰N和末端炔烃的 可见光驱动铜催化有氧氧化级联环化：3-芳基香豆素的区域选择性合成†

  摘要：

  我们提出了可持续的，直观的，高度区域选择性的，可见光驱动的铜催化的N-甲苯磺酰with与末端炔烃的有氧氧化级联环化反应，以在室温下制备3-芳基香豆素。这种操作简单的方法已成功应用于各种N-甲苯磺酰hydr和炔烃（49个实例），并且进展顺利，可提供具有生物活性的化合物，例如单胺氧化酶B（MAO-B）抑制剂和辣根过氧化物酶（HRP）抑制剂，在温和的条件下具有令人满意的产量。此外，机理研究表明，反应是通过铜进行的（II18 O 2同位素标记实验证明）-超氧或-过氧配合物介导的末端炔烃的氧化环化反应。

  DOI：

  10.1039/c9cc01801h

文献信息

• [EN] LABELLED COUMARIN DERIVATIVES<br/>[FR] DÉRIVÉS DE COUMARINE MARQUÉS
  申请人：GE HEALTHCARE LTD

  公开号：WO2016097339A1

  公开（公告）日：2016-06-23

  The present invention relates to compounds having selective binding for MAO-B as compared with MAO-A. The invention also provides radioactive versions of these compounds, and precursor compounds for the synthesis of these radioactive compounds. The radioactive compounds of the invention can find use for in vivo imaging applications.

  本发明涉及与MAO-A相比具有选择性结合MAO-B的化合物。该发明还提供这些化合物的放射性版本，以及用于合成这些放射性化合物的前体化合物。本发明的放射性化合物可用于体内成像应用。
• Insight into the Functional and Structural Properties of 3-Arylcoumarin as an Interesting Scaffold in Monoamine Oxidase B Inhibition
  作者：Maria João Matos、Santiago Vilar、Verónica García-Morales、Nicholas P. Tatonetti、Eugenio Uriarte、Lourdes Santana、Dolores Viña

  DOI：10.1002/cmdc.201300533

  日期：2014.7

  halogenated 3‐arylcoumarins were carried out with the aim of finding new structural and biological features. This series displays several alkyl, hydroxy, halogen, and/or alkoxy groups in both benzene rings of the 3‐arylcoumarin scaffold. Most of the compounds studied show high affinity and selectivity for the human monoamine oxidase B (hMAO‐B) isoenzyme, with IC50 values in the low nanomolar and picomolar range

  为了发现新的结构和生物学特征，进行了一系列新的卤代3-芳基香豆素的设计，合成，药理学评价和理论研究。该系列在3-芳基香豆素骨架的两个苯环中都显示几个烷基，羟基，卤素和/或烷氧基。研究的大多数化合物对人单胺氧化酶B（hMAO-B）同工酶显示出高亲和力和选择性，IC 50值在低纳摩尔和皮摩尔范围内。大多数评估的化合物显示出比司来吉兰（参考化合物）更高的MAO-B抑制活性和选择性。香豆素12（3-（3-溴苯基）-6-甲基香豆素）是活性最高的化合物（IC 50 = 134 p M），其活性是司来吉兰的140倍，对hMAO-B的特异性最高。为了更好地理解结构与活性之间的关系，对人单胺氧化酶（A和B）的结构进行了对接实验。最后，基于计算机生成的理化描述符，对被动血脑分区进行了预测。
• Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors
  作者：Maria Joao Matos、Dolores Viña、Carmen Picciau、Francisco Orallo、Lourdes Santana、Eugenio Uriarte

  DOI：10.1016/j.bmcl.2009.07.039

  日期：2009.9

  A series of 6-methyl-3-phenylcoumarins 3-6 were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. A comparative study between the three possible mono methoxy 3-phenyl derivatives and the p-hydroxy analogue is reported. The synthesis of these new resveratrol-coumarin hybrids was carried out by a Perkin reaction between the 5-methylsalicylaldehyde and the corresponding

  合成了一系列6-甲基-3-苯基香豆素3-6，并作为单胺氧化酶A和B（MAO-A和MAO-B）抑制剂进行了评估。报道了三种可能的单甲氧基3-苯基衍生物与对羟基类似物的比较研究。这些新的白藜芦醇-香豆素杂化物的合成是通过5-甲基水杨醛和相应的苯乙酸之间的珀金反应进行的。该p取代的化合物-甲氧基3水解成6通过用氢碘酸传统反应。制备的化合物对MAO-B同工酶具有很高的选择性，其中一些IC 50值在低纳摩尔范围内。化合物4，其中甲氧基位于间位，是该系列中最活跃的，对MAO-B的IC 50为0.80 nM，并且比R -（-）-去异戊二烯基（参考化合物）。
• Comparative study of the 3-phenylcoumarin scaffold: Synthesis, X-ray structural analysis and semiempirical calculations of a selected series of compounds
  作者：Maria J. Matos、Santiago Vilar、Nicholas P. Tatonetti、Lourdes Santana、Eugenio Uriarte

  DOI：10.1016/j.molstruc.2013.07.037

  日期：2013.10

  comparative study between compounds 1, 2 and 3, based on the structural results, was carried out. In addition, the X-ray structures were compared to those obtained combining conformational analysis with semiempirical methodologies (AM1 and PM3). The results provided by the semiempirical calculations in gas phase are in strong agreement with the X-ray method for the three molecules under study, meaning

  摘要 通过 Perkin 反应合成了化合物 1（6-甲基-3-苯基香豆素）、2（3-（邻甲氧基苯基）-6-甲基香豆素）和 3（3-（间甲氧基苯基）-6-甲基香豆素）。 2-羟基-5-甲基苯甲醛和相应的苯乙酸。1H 和 13C NMR 和 X 射线衍射测定了衍生物的分子结构。基于结构结果，对化合物 1、2 和 3 进行了比较研究。此外，将 X 射线结构与结合构象分析和半经验方法（AM1 和 PM3）获得的结构进行了比较。气相半经验计算提供的结果与所研究的三个分子的 X 射线方法非常一致，
• Remarkable antioxidant properties of a series of hydroxy-3-arylcoumarins
  作者：Maria João Matos、Fernanda Pérez-Cruz、Saleta Vazquez-Rodriguez、Eugenio Uriarte、Lourdes Santana、Fernanda Borges、Claudio Olea-Azar

  DOI：10.1016/j.bmc.2013.04.015

  日期：2013.7

  In the present work we synthesized a series of hydroxy-3-arylcoumarins (compounds 1-9), some of them previously described as MAO-B selective inhibitors, with the aim of evaluating their antioxidant properties. Theoretical evaluation of ADME properties of all the derivatives was also carried. out. From the ORAC-FL, ESR and CV data it was concluded that these derivatives are very good antioxidants, with a very interesting hydroxyl, DPPH and superoxide radicals scavenging profiles. In particular compound 9 is the most active and effective antioxidant of the series (ORAC-FL = 13.5, capacity of scavenging hydroxyl radicals = 100%, capacity of scavenging DPPH radicals = 65.9% and capacity of scavenging superoxide radicals = 71.5%). Kinetics profile for protection fluorescein probe against peroxyl radicals by addition of antioxidant molecule 9 was also performed. Therefore, it can operate as a potential candidate for preventing or minimizing the free radicals overproduction in oxidative-stress related diseases. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.