7-羟基-4-甲基-8-(哌啶-1-基甲基)-2H-色烯-2-酮 | 10549-62-9

• 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
• 中文名称: 7-羟基-4-甲基-8-(哌啶-1-基甲基)-2H-色烯-2-酮
• 英文名称: 7-hydroxy-4-methyl-8-(piperidinomethyl)coumarin
• 英文别名: 7-hydroxy-4-methyl-8-piperidin-1-ylmethylchromen-2-one；7-hydroxy-4-methyl-8-(piperidin-1-ylmethyl)-2H-chromen-2-one；7-Hydroxy-4-methyl-8-piperidinomethyl-cumarin；8-Piperidinomethyl-7-hydroxy-4-methyl-cumarin；4-Methyl-2-oxo-8-(piperidin-1-ium-1-ylmethyl)chromen-7-olate
• CAS: 10549-62-9
• 化学式: C₁₆H₁₉NO₃
• mdl: MFCD00583538
• 分子量: 273.332
• InChiKey: DIJMIZCQAHRDQL-UHFFFAOYSA-N

物化性质

• 熔点：
  138 °C(Solv: ethanol (64-17-5))
• 沸点：
  460.3±45.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  羟甲香豆素	7-hydroxy-4-methyl-chromen-2-one	90-33-5	C10H8O3	176.172

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	4-Methyl-8-(piperidin-1-ylmethyl)-7-propoxychromen-2-one	1024743-12-1	C19H25NO3	315.412
  ——	5-[4-methyl-8-[(2-methyl-1H-indol-3-yl)methyl]-2-oxochromen-7-yl]oxy-5-oxopentanoic acid	1024743-64-3	C25H23NO6	433.461

反应信息

• 作为反应物：
  描述：

  7-羟基-4-甲基-8-(哌啶-1-基甲基)-2H-色烯-2-酮 、 2-(diethylamino)-7-methoxychromone 在 乙酸酐 作用下， 反应 1.5h， 以58%的产率得到2-(Diethylamino)-3-[(7-hydroxy-4-methyl-2-oxochromen-8-yl)methyl]-7-methoxychromen-4-one
  参考文献：
  名称：

  苯并吡喃的不对称亚甲基衍生物对嗜中性白细胞O（2）（-）的抑制作用：用作潜在的消炎药。

  摘要：

  合成并测试了苯并吡喃9的一些不对称衍生物，以验证其对PKC的抑制活性。为此，在乙酸存在下，用2-（二烷基氨基）苯并吡喃-4-酮或3-（二烷基氨基）萘并[2,1-b]吡喃-1-酮8处理7-羟基香豆素6的曼尼希碱。用丙酸酐或丙酸酐产生化合物9。用PMA和f-MLF刺激的人类嗜中性粒细胞用作细胞模型。化合物9的效率建立在其减少活化的人类嗜中性粒细胞产生O（2）（-）的能力上。在色酮部分的7位带有乙酰氧基的化合物9d和9f似乎有效地抵消了中性粒细胞的活化。

  DOI：

  10.1016/s0223-5234(01)01279-x
• 作为产物：
  描述：

  间苯二酚 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 7-羟基-4-甲基-8-(哌啶-1-基甲基)-2H-色烯-2-酮
  参考文献：
  名称：

  哌嗪和哌啶取代的 7-羟基香豆素用于抗炎剂的开发

  摘要：

  香豆素 (2 H-1-benzopyran-2-one) 是可从多种植物中分离出来的衍生物，据报道具有抗凝、抗菌、抗炎或抗癌活性。其中一些结构目前已被批准用于治疗心血管疾病，如抗生素或抗癌药物。鉴于这种结构的巨大潜力和有限的研究集中于苯并吡喃酮杂环的碳 8 衍生的分子，我们在这个项目中合成了 38 种香豆素衍生物，通过用一些芳香族和脂肪族取代的哌啶取代苯并吡喃环的碳 8 和哌嗪类。由于其中一些结构已经显示出一些碳酸酐酶 (CA) 抑制作用，并且据报道 CA 酶与炎症密切相关，合成的衍生物在体外评估了它们的抗炎活性。结果表明化合物20和31显示出有希望的抗炎活性，因为它们表现出比参考药物更好的活性。

  DOI：

  10.1002/ardp.202000354

文献信息

• Mannich bases of hydroxycoumarins: synthesis, DFT/QTAIM computational study and assessment of biological activity
  作者：J. Sergio Durand-Niconoff、Erik Ortiz-Blanco、Gabriela Sosa-Ortiz、José L. Olivares-Romero、Enrique Juárez-Aguilar、Eva Luz Montoya-Hernández、Cynthia Fernández-Pomares、Ricardo Tovar-Miranda、María Eugenia Castro、Francisco J. Melendez、Tomás Guerrero

  DOI：10.1039/d1ra04611j

  日期：——

  The synthesis of six Mannich bases derived from hydroxycoumarins was carried out in moderate yields, two of these derivatives were described for the first time. Conformational analysis was performed through DFT theoretical calculations explaining the formation of stable six membered rings based on intramolecular hydrogen bonds within the structure. These findings were correlated with the antiproliferative

  由羟基香豆素衍生的六种曼尼希碱基的合成以中等收率进行，其中两种衍生物首次被描述。通过 DFT 理论计算进行构象分析，解释了基于结构内分子内氢键形成稳定的六元环。这些发现与抗增殖活性相关。首次描述了曼尼希碱基通过其在 HeLa 癌细胞系中的抗增殖活性的生物活性，表明该化合物能够抑制宫颈癌的增殖超过 60%。同样，光物理特性的理论建模也取得了可喜的成果，
• Ghantwal; Samant, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 11, p. 1242 - 1247
  作者：Ghantwal、Samant

  DOI：——

  日期：——
• Activity of Mannich bases of 7-hydroxycoumarin against Flaviviridae
  作者：Mauro Mazzei、Erika Nieddu、Mariangela Miele、Alessandro Balbi、Marco Ferrone、Maurizio Fermeglia、Marco T. Mazzei、Sabrina Pricl、Paolo La Colla、Fabio Marongiu、Cristina Ibba、Roberta Loddo

  DOI：10.1016/j.bmc.2007.11.045

  日期：2008.3

  Some Mannich bases of 7-hydroxycoumarin (2) and their simple derivatives (3 and 4) were prepared and tested against viruses containing single-stranded, positive-sense RNA genomes (ssRNA(+)). This study was directed toward Flaviviridae and, in particular, HCV surrogate viruses (BVDV, YFV). The 7-hydroxy derivatives 2 were generally devoid of activity, but when position 7 was propylated, the resulting 7-propyloxy derivatives 3 were in some cases endowed with an interesting activity against BVDV. The formation of 7-benzoyl derivatives 4 gave compounds generally lacking in activity against Flaviviridae, whereas the appearance of activity against RSV has been observed. Also some unsymmetrical methylene derivatives 5-7 (namely coumarins bridged to chromones or indoles) were found moderately active in antiviral tests. Derivatives 3 were submitted to a molecular modeling study using DNA polymerase of HCV as a target. The good correlation between calculated molecular modeling IC50 and experimental EC50 indicates that DNA polymerase is potentially involved in the inhibition of surrogate HCV viruses. (C) 2007 Elsevier Ltd. All rights reserved.
• 2-(Dialkylamino)-4H-1-benzopyran-4-one derivatives modify chloride conductance in CFTR expressing cells
  作者：Mauro Mazzei、Erika Nieddu、Chiara Folli、Emanuela Caci、Louis V.J Galietta

  DOI：10.1016/s0014-827x(03)00155-1

  日期：2003.9

  Some 2-(diethylamino)-7-hydroxy-4H-1-benzopyran-4-one derivatives, potentially useful as activators of the cystic fibrosis transmembrane conductance regulator (CFTR), were prepared. The synthesized compounds were tested, together with others 2-(dialkylamino)-7-hydroxybenzopyran-4-one derivatives, by measuring their capacity to modify the kinetics of iodide influx in Fisher rat thyroid cells expressing wild type CFTR and the halide-sensitive yellow fluorescent protein. Among the tested compounds the dinitrile derivatives 8 and 9 are endowed with an activity comparable to the reference compound apigenin.
• Unsymmetrical methylene derivatives of indoles as antiproliferative agents
  作者：M Mazzei

  DOI：10.1016/s0223-5234(01)01286-7

  日期：2001.12.1

  Indole-3-carbinol is a natural product which has been shown to reduce the incidence of spontaneous and carcinogen-induced mammary tumours in animals, Eighteen unsymmetrical methylene derivatives of indoles were prepared by reaction of Mannich bases of 7-hydroxycoumarins with substituted indoles in acetic or propionic anhydride. The synthesised molecules were tested in vitro against the MCF7 and MDA-MB-231 breast cancer cell lines by MTT and cell count assays. Results from 16 tested compounds showed that 60% of them exerted some effects against the MDA-MB-231 compared to about 30% towards the MCF7. Among all, the 3-(7'-acetoxy-4-methylcoumarin-8'-yl)methyl-2-methylindole resulted the most effective in both cell lines, compared to indole-3-carbinol, In conclusion, these preliminary results report that some of these compounds might be promising potential antiproliferative agents. (C) 2001 Editions scientifiques et medicales Elsevier SAS.