7-[(4-methoxybenzyl)oxy]-2H-chromen-2-one | 374768-02-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-[(4-methoxybenzyl)oxy]-2H-chromen-2-one
• 英文别名: 7-(p-methoxybenzyloxy)coumarin；7-[(4-methoxyphenyl)methoxy]chromen-2-one
• CAS: 374768-02-2
• 化学式: C₁₇H₁₄O₄
• mdl: MFCD02185330
• 分子量: 282.296
• InChiKey: WFDFKHSTSZLDJM-UHFFFAOYSA-N

物化性质

• 沸点：
  476.4±45.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-[(4-methoxybenzyl)oxy]-2H-chromen-2-one 在 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  Synthesis and Biological Evaluation ofortho-ArylN-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors

  摘要：

  AbstractHistone deacetylases (HDACs) are a family of enzymes that play a crucial role in biological process and diseases. In contrast to other isozymes, HDAC8 is uniquely incapable of histone acetylation. In order to delineate its physiological function, we developed HDAC8‐selective inhibitors using knowledge‐based design combined with structural modeling techniques. Enzyme inhibitory analysis demonstrated that some of the resulting compounds (22 b, 22 d, 22 f, and 22 g) exhibited anti‐HDAC8 activity superior to PCI34051, a known HDAC8‐specific inhibitor, with IC50 values in the range of 5–50 nM. Among them, compound 22 d showed antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1‐5); it exhibited cytotoxicity against human lung CL1‐5 cells similar to that of SAHA yet without significant cytotoxicity for normal IMR‐90 cells. Expression profiling of HDAC isoforms in three cancer cell lines indicated that the HDAC8 level in CL1‐5 is higher than that in H1299 and CL1‐1 cells, a result consistent with the differential cytotoxicity of compound 22 d. These results suggest the effectiveness of our design concept, which may lead to a tool compound for studying the specific role of HDAC8 in cellular biological processes.

  DOI：

  10.1002/cmdc.201200300
• 作为产物：
  描述：

  7-羟基香豆素 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-[(4-methoxybenzyl)oxy]-2H-chromen-2-one
  参考文献：
  名称：

  Inhibitory Effects of 6-Alkoxycoumarin and 7-Alkoxycoumarin Derivatives on Lipopolysaccharide/Interferon γ-Stimulated Nitric Oxide Production in RAW264 Cells

  摘要：

  众所周知，香豆素及其衍生物具有抗炎和抗氧化作用。在这项研究中，我们从市售的 6-羟基香豆素（6HC）和 7-羟基香豆素（7HC）中合成了 32 种香豆素衍生物，并考察了它们对鼠巨噬细胞 RAW264 在脂多糖/干扰素γ（LPS/IFNγ）刺激下产生一氧化氮（NO）的影响。在这些衍生物中，6HC-8（6-(3-苯基丙氧基)香豆素）、6HC-14（6-(2-辛炔氧基)香豆素）、7HC-14（7-(2-辛炔氧基)香豆素）和 7HC-16（7-(3,5-二甲氧基苄氧基)香豆素）在低浓度（25 µ<小>M<小>）下明显抑制了一氧化氮的产生。这些合成的香豆素衍生物也明显抑制了诱导型 NO 合酶（iNOS）蛋白和 mRNA 的表达，这可以通过 Western 印迹和定量实时聚合酶链反应（RT-PCR）进行评估。

  DOI：

  10.1248/bpb.35.963

文献信息

• Synthesis and bioactivity of novel coumarin derivatives
  作者：Sai-Yang Zhang、Dong-Jun Fu、Hui-Hui Sun、Xiao-Xin Yue、Ying-Chao Liu、Yan-Bing Zhang、Hong-Min Liu

  DOI：10.1007/s10593-016-1898-3

  日期：2016.6

  A series of novel coumarin derivatives were synthesized from commercially available chemical agents. All prepared compounds were evaluated for their in vitro antiproliferative activity against five selected human cancer cell lines (EC109, MGC-803, PC-3, MCF-7, and EC9706) and their in vitro antimicrobial activity against E. coli and M. albicans. 4-(3-Bromopropoxy)-2H-chromen-2-one exhibited the highest

  从市售化学试剂合成了一系列新型香豆素衍生物。所有制备的化合物为他们进行了评价的体外抗增殖活性对五种选择的人类癌细胞系（EC109，MGC-803，PC-3，MCF-7，和EC9706）和它们的体外抗微生物活性的大肠杆菌和M.白色念珠菌。4-（3-溴丙氧基）-2- ħ -色烯-2-酮表现出对MGC-803细胞系的最高生长抑制（IC 50 47.7μM）和7-（2-溴乙氧基）-2- ħ -苯并吡喃-2-酮对MCF-7细胞系表现出最高的生长抑制作用（IC 50 48.3μM）。后一种化合物对大肠杆菌（MIC 50 0.27μg/ ml）。
• Structure–activity relationships for naturally occurring coumarins as β-secretase inhibitor
  作者：Shinsuke Marumoto、Mitsuo Miyazawa

  DOI：10.1016/j.bmc.2011.12.002

  日期：2012.1

  The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of β-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen

  本研究证明可以评估天然香豆素（NOC）（包括简单香豆素，呋喃香豆素和吡喃香豆素）对β-分泌酶（BACE1）活性的抑制作用。在41个NOC中，一些呋喃香豆素抑制了BACE1的活性，但简单的香豆素和吡喃香豆素没有影响。最有效的抑制剂是5-香叶基氧基-8-甲氧基补骨脂素（31），IC 50值为9.9μM 。其他呋喃香豆素衍生物，例如8-香叶基氧基-5-甲氧基补骨脂素（35），8-香叶基氧基补骨脂蛋白（24）和佛手柑（18）抑制BACE1活性，IC 50值<25.0μM。通过狄克逊曲线和Cornish-鲍登地块抑制机制的分析表明，化合物18，31和35混合型抑制剂。香豆素24抑制BACE1的动力学是非竞争性抑制剂。