3-(chloromethyl)-6-methylcoumarin | 1274898-29-1

• 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: 3-(chloromethyl)-6-methylcoumarin
• 英文别名: 3-(chloromethyl)-6-methylchromen-2-one
• CAS: 1274898-29-1
• 化学式: C₁₁H₉ClO₂
• 分子量: 208.644
• InChiKey: RZYUQZNNVKWOMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.84
• 重原子数：
  14.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  30.21
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-(chloromethyl)-6-methylcoumarin 、 4-甲氧基苯硼酸 在 palladium diacetate 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以93%的产率得到
  参考文献：
  名称：

  Suzuki偶联反应合成3-苄基香豆素

  摘要：

  香豆素是众多天然产物 1 中的结构支架，也是众所周知的含氧杂环之一，具有多种生物活性。2 此外，它们已在技术应用 3 中发现并用作合成重要分子的中间体。4 由于它们的多种应用，香豆素的各种经典路线 5 如 Pechmann、Knoevenagel、Perkin、Reformatsky 和 ​​Wittig 缩合反应已被报道。然而，这些方法都存在反应条件苛刻、多步合成或化学收率低等问题。为了克服与这些经典方法相关的问题，最近开发了许多通过直接环形成 6 和香豆素衍生物 7,8 的金属催化偶联反应来方便和通用合成香豆素衍生物的策略。在香豆素衍生物中，包括苄基香豆素在内的3-烷基香豆素是重要的组成部分，并显示出重要的生物活性。9 例如，华法林是一种 3 苄基香豆素衍生物，是最广泛使用的口服抗凝剂。10 3-烷基香豆素的新的、方便的、通用的合成方法已被开发出来。9 瓦迪亚等人。报道了由酰胺和 POCl3

  DOI：

  10.5012/bkcs.2011.32.8.2897

文献信息

• Chikungunya virus inhibition by synthetic coumarin–guanosine conjugates
  作者：Jih Ru Hwu、Wen-Chieh Huang、Shu-Yu Lin、Kui-Thong Tan、Yu-Chen Hu、Fa-Kuen Shieh、Sergey O. Bachurin、Alexey Ustyugov、Shwu-Chen Tsay

  DOI：10.1016/j.ejmech.2019.01.037

  日期：2019.3

  lack of effective vaccines and antiviral drugs to intervene this disease, 21 new conjugated compounds were designed and synthesized by coupling of 6,8-dithioguanosine at its C-6 position with 3-(chloromethyl)coumarins bearing an F, Cl, Br, Me, or –OMe substituent through the –SCH2– joint. Meanwhile, an organic “dummy” ligand (e.g., methyl, benzyl, and naphthylmethyl) or a coumarinyl moiety was attached

  自1952年在非洲坦any尼喀（Tanganyika）发现以来，基孔肯雅病毒（CHIKV）暴发已在非洲，亚洲，欧洲和美洲发生。直到现在，基孔肯雅热已在近40个国家蔓延。由于缺乏有效的疫苗和抗病毒药物来干预该疾病，因此设计并合成了21种新的共轭化合物，方法是将C-6位的6,8-二硫代鸟苷与带有F，Cl，Br的3-（氯甲基）香豆素偶联，Me或–OMe取代基通过–SCH 2 –接头。同时，有机“虚拟”配体（例如，甲基，苄基和萘甲基）或香豆素基部分连接在C-8位置。通过高通量筛选，发现这些新结合物中的三种可有效抑制Vero细胞中的CHIKV（EC 50 = 9.9–13.9μM），并且显示出低毒性（CC 50  = 96.5–212μM）。选择性指数值为9.37–21.7。推导了它们的结构-活性关系，这表明香豆素部分是必不可少的，并且-OMe基团的存在增强了抗病毒活性。
• Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus
  作者：Shwu-Chen Tsay、Shu-Yu Lin、Wen-Chieh Huang、Ming-Hua Hsu、Kuo Hwang、Chun-Cheng Lin、Jia-Cherng Horng、I-Chia Chen、Jih Hwu、Fa-Kuen Shieh、Pieter Leyssen、Johan Neyts

  DOI：10.3390/molecules21020228

  日期：——

  experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC50 values (5.1-8.4 μM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus

  以咪唑和香豆素衍生物为原料，通过化学方法合成了一系列带有-SCH2-键的新型共轭化合物。实验结果表明，在二十种新合成的咪唑-香豆素缀合物中，其中三种表现出吸引人的 EC50 值 (5.1-8.4 μM) 和针对丙型肝炎病毒的选择性指数 >20。通过用两个因素修改其结构，它们的效力和选择性得到显着提高：在 N(1) 位置带有氢原子的咪唑核和带有取代基（例如 Cl、F、Br、Me 和 OMe）的香豆素核。这些指南为进一步开发作为抗病毒剂的共轭化合物提供了有价值的信息。
• Development of New Sulfur-Containing Conjugated Compounds as Anti-HCV Agents
  作者：Jih Ru Hwu、Shu-Yu Lin、Shwu-Chen Tsay、Raghunath Singha、Benoy Kumar Pal、Pieter Leyssen、Johan Neyts

  DOI：10.1080/10426507.2010.520284

  日期：2011.5.1

  Various conjugated compounds containing a coumarin moiety and a heterocyclic nucleus were synthesized. Their activity against hepatitis C virus was tested on subgenomic replicon replication in Huh 5-2 cells. Some heterobicycle-coumarin conjugates with the -S-CH2-linker were found to possess appealing antiviral activities. The sulfur atom in these conjugated compounds was found to be an essential element to their antiviral activity.
• Coumarin−Purine Ribofuranoside Conjugates as New Agents against Hepatitis C Virus
  作者：Jih Ru Hwu、Shu-Yu Lin、Shwu-Chen Tsay、Erik De Clercq、Pieter Leyssen、Johan Neyts

  DOI：10.1021/jm101337v

  日期：2011.4.14

  About 3% of world's population is infected by the hepatitis C virus (HCV), for which prophylactic vaccine is not available yet. Nowadays, pegylated interferon-a and ribavirin are commonly used to treat HCV; unfortunately these drugs often produce significant side effects. Upon the desperate need of anti-HCV drugs, a plan to establish a new compound library was set that included leads with high antiviral activity, good hydrophilicity, yet low toxicity. Accordingly, 26 new conjugated compounds were synthesized through the chemical coupling of various 9-(beta-D-ribofuranosyl)purine-8-thiones with 3-(chloromethyl)coumarins bearing various substitucnts. A -SCH2- unit was used to link the coumarin and the purine moieties. The three hydroxyl groups at the 2'-, 3'-, and 5'-positions were selectively protected with an acyl or acetal group in these coumarin-purine ribofuranosides. Their anti-HCV and cytostatic determination assays were performed, and the structure activity relationship was established. Three conjugates in the family of 8-(coumarin-3'-yl)methylthio-9-(beta-D-ribofuranos-1 ''-yl)purine possessed an appealing ability to inhibit HCV replication with EC50 between 5.5 and 6.6 mu M and EC90 of similar to 20 mu M. These data in the new compound library provide clues for the future in the development of anti-HCV leads for viral eradication.