1,2-dimethoxy-3-(2-methoxy-4-propylphenoxy)-5-propylbenzene

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: 1,2-dimethoxy-3-(2-methoxy-4-propylphenoxy)-5-propylbenzene
• 英文别名: 1,2-Dimethoxy-3-(2-methoxy-4-propylphenoxy)-5-propylbenzene
• 化学式: C₂₁H₂₈O₄
• 分子量: 344.451
• InChiKey: DLYMXJXGKUTWGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  丁香酚 在 盐酸 、 四甲基乙二胺 、 丙二酸二叔丁酯 、 Pd/C (30%) 、 氢气 、 仲丁基锂 、 potassium carbonate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 1,2-dimethoxy-3-(2-methoxy-4-propylphenoxy)-5-propylbenzene
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship of Dehydrodieugenol B Neolignans against Trypanosoma cruzi

  摘要：

  Trypanosoma cruzi is the etiologic agent of Chagas disease, which affects over seven million people, especially in developing countries. Undesirable side effects are frequently associated with current therapies, which are typically ineffective in the treatment of all stages of the disease. Here, we report the first synthesis of the neolignan dehydrodieugenol B, a natural product recently shown to exhibit activity against T. cruzi. Using this strategy, a series of synthetic analogues were prepared to explore structure-activity relationships. The in vitro antiparasitic activities of these analogues revealed a wide tolerance of modifications and substituent deletions, with maintained or improved bioactivities against the amastigote forms of the parasite (50% inhibitory concentration (IC₅₀) of 4-63 μM) and no mammalian toxicity (50% cytotoxic concentration (CC₅₀) of >200 μM). Five of these analogues meet the Drugs for Neglected Disease Initiative (DNDi) "hit criteria" for Chagas disease. This work has enabled the identification of key structural features of the natural product and sites where scaffold modification is tolerated.

  DOI：

  10.1021/acsinfecdis.0c00523

文献信息

• Dehydrodieugenol B derivatives as antiparasitic agents: Synthesis and biological activity against Trypanosoma cruzi
  作者：Daiane D. Ferreira、Fernanda S. Sousa、Thais A. Costa-Silva、Juliana Q. Reimão、Ana C. Torrecilhas、Deidre M. Johns、Claire E. Sear、Kathia M. Honorio、João Henrique G. Lago、Edward A. Anderson、Andre G. Tempone

  DOI：10.1016/j.ejmech.2019.05.001

  日期：2019.8

  semi-synthetic library of twenty-three neolignan derivatives was prepared to explore synthetically accessible structure activity relationships (SAR) against Trypanosoma cruzi. Five compounds demonstrated activity against trypomastigotes (IC50 values from 8 to 64 μM) and eight showed activity against intracellular amastigotes (IC50 values from 7 to 16 μM). Eighteen derivatives demonstrated no mammalian cytotoxicity

  恰加斯病是一种被忽视的原生动物疾病，在发展中国家影响超过800万人。由于当前使用的疗法的数量和毒性特征有限，因此迫切需要新药。在以往的研究中，我们报道了两个相关的抗锥体新木脂体的隔离Nectandra leucantha（樟科）。在这项工作中，准备了二十三种新木脂素衍生物的半合成文库，以探索针对克鲁氏锥虫的合成可及结构活性关系（SAR）。五个化合物显示出对锥虫病的活性（IC 50值为8至64μM），八个化合物显示了对胞内变形虫的活性（IC 50值介于7至16μM之间）。十八种衍生物没有显示出对哺乳动物最大200μM的细胞毒性。天然脱氢丁香酚B的酚醛乙酸酯衍生物对两种寄生虫形式均有效，并消除了巨噬细胞内100％的amastigotes。该化合物导致线粒体膜电位快速而强烈地去极化，并观察到细胞内活性氧水平降低。荧光分析表明，该衍生物既不影响寄生质膜的通透性，也不影响其电势，扫描电子显微镜研究也
• Synthesis and Structure–Activity Relationship of Dehydrodieugenol B Neolignans against <i>Trypanosoma cruzi</i>
  作者：Claire E. Sear、Pauline Pieper、Maiara Amaral、Maiara M. Romanelli、Thais A. Costa-Silva、Marius M. Haugland、Joseph A. Tate、João H. G. Lago、Andre G. Tempone、Edward A. Anderson

  DOI：10.1021/acsinfecdis.0c00523

  日期：2020.11.13

  Trypanosoma cruzi is the etiologic agent of Chagas disease, which affects over seven million people, especially in developing countries. Undesirable side effects are frequently associated with current therapies, which are typically ineffective in the treatment of all stages of the disease. Here, we report the first synthesis of the neolignan dehydrodieugenol B, a natural product recently shown to exhibit activity against T. cruzi. Using this strategy, a series of synthetic analogues were prepared to explore structure-activity relationships. The in vitro antiparasitic activities of these analogues revealed a wide tolerance of modifications and substituent deletions, with maintained or improved bioactivities against the amastigote forms of the parasite (50% inhibitory concentration (IC₅₀) of 4-63 μM) and no mammalian toxicity (50% cytotoxic concentration (CC₅₀) of >200 μM). Five of these analogues meet the Drugs for Neglected Disease Initiative (DNDi) "hit criteria" for Chagas disease. This work has enabled the identification of key structural features of the natural product and sites where scaffold modification is tolerated.