(E)-1-(2-hydroxy-5-methoxyphenyl)-3-(1H-indol-3-yl)prop-2-en-1-one | 1216936-77-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (E)-1-(2-hydroxy-5-methoxyphenyl)-3-(1H-indol-3-yl)prop-2-en-1-one
• CAS: 1216936-77-4
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: JCZLGRSZTAYIRZ-SOFGYWHQSA-N

物化性质

• 熔点：
  120 °C(Solvent: Methanol)
• 沸点：
  569.3±50.0 °C(predicted)
• 密度：
  1.305±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-1-(2-hydroxy-5-methoxyphenyl)-3-(1H-indol-3-yl)prop-2-en-1-one 在 双氧水 、 三溴化硼 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 48.0h， 生成 3,6-dihydroxy-2-(1H-indol-3-yl)-4H-chromen-4-one
  参考文献：
  名称：

  Discovery of a benzothiophene-flavonol halting miltefosine and antimonial drug resistance in Leishmania parasites through the application of medicinal chemistry, screening and genomics

  摘要：

  Leishmaniasis, a major health problem worldwide, has a limited arsenal of drugs for its control. The appearance of resistance to first- and second-line anti-leishmanial drugs confirms the need to develop new and less toxic drugs that overcome spontaneous resistance. In the present study, we report the design and synthesis of a novel library of 38 flavonol-like compounds and their evaluation in a panel of assays encompassing parasite killing, pharmacokinetics, genomics and ADME-Toxicity resulting in the progression of a compound in the drug discovery value chain. Compound 19, 2-(benzo[b]thiophen-3-yl)3-hydroxy-6-methoxy-4H-chromen-4-one, exhibited a broad-spectrum activity against Leishmania spp. (EC50 1.9 mu M for Leishmania infantum, 3.4 mu M 4 for L. donovani, 6.7 mu M for L. major), Trypanosoma cruzi (EC50 7.5 mu M) and T. brucei (EC50 0.8 mu M). Focusing on anti-Leishmania activity, compound 19 challenge in vitro did not select for resistance markers in L donovani, while a Cos-Seq screening for dominant resistance genes identified a gene locus on chromosome 36 that became ineffective at concentrations beyond EC50 Thus, compound 19 is a promising scaffold to tackle drug resistance in Leishmania infection. In vivo pharmacokinetic studies indicated that compound 19 has a long half-life (intravenous (IV): 63.2 h; per os (PO): 46.9 h) with an acceptable ADME-Toxicity profile. When tested in Leishmania infected hamsters, no toxicity and limited efficacy were observed. Low solubility and degradation were investigated spectroscopically as possible causes for the sub-optimal pharmacokinetic properties. Compound 19 resulted a specific compound based on the screening against a protein set, following the intrinsic fluorescence changes. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111676
• 作为产物：
  描述：

  3-吲哚甲醛 、 2'-羟基-5'-甲氧基苯乙酮 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 (E)-1-(2-hydroxy-5-methoxyphenyl)-3-(1H-indol-3-yl)prop-2-en-1-one
  参考文献：
  名称：

  Venkatesan; Maruthavanan, Asian Journal of Chemistry, 2011, vol. 23, # 5, p. 2121 - 2124

  摘要：

  DOI：

文献信息

• Venkatesan; Maruthavanan, Bulletin of the Chemical Society of Ethiopia, 2011, vol. 25, # 3, p. 419 - 425
  作者：Venkatesan、Maruthavanan

  DOI：——

  日期：——
• Discovery of a benzothiophene-flavonol halting miltefosine and antimonial drug resistance in Leishmania parasites through the application of medicinal chemistry, screening and genomics
  作者：Chiara Borsari、María Dolores Jiménez-Antón、Julia Eick、Eugenia Bifeld、Juan José Torrado、Ana Isabel Olías-Molero、María Jesús Corral、Nuno Santarem、Catarina Baptista、Leda Severi、Sheraz Gul、Markus Wolf、Maria Kuzikov、Bernhard Ellinger、Jeanette Reinshagen、Gesa Witt、Pasquale Linciano、Annalisa Tait、Luca Costantino、Rosaria Luciani、Paloma Tejera Nevado、Dorothea Zander-Dinse、Caio H. Franco、Stefania Ferrari、Carolina B. Moraes、Anabela Cordeiro-da-Silva、Glauco Ponterini、Joachim Clos、José María Alunda、Maria Paola Costi

  DOI：10.1016/j.ejmech.2019.111676

  日期：2019.12

  Leishmaniasis, a major health problem worldwide, has a limited arsenal of drugs for its control. The appearance of resistance to first- and second-line anti-leishmanial drugs confirms the need to develop new and less toxic drugs that overcome spontaneous resistance. In the present study, we report the design and synthesis of a novel library of 38 flavonol-like compounds and their evaluation in a panel of assays encompassing parasite killing, pharmacokinetics, genomics and ADME-Toxicity resulting in the progression of a compound in the drug discovery value chain. Compound 19, 2-(benzo[b]thiophen-3-yl)3-hydroxy-6-methoxy-4H-chromen-4-one, exhibited a broad-spectrum activity against Leishmania spp. (EC50 1.9 mu M for Leishmania infantum, 3.4 mu M 4 for L. donovani, 6.7 mu M for L. major), Trypanosoma cruzi (EC50 7.5 mu M) and T. brucei (EC50 0.8 mu M). Focusing on anti-Leishmania activity, compound 19 challenge in vitro did not select for resistance markers in L donovani, while a Cos-Seq screening for dominant resistance genes identified a gene locus on chromosome 36 that became ineffective at concentrations beyond EC50 Thus, compound 19 is a promising scaffold to tackle drug resistance in Leishmania infection. In vivo pharmacokinetic studies indicated that compound 19 has a long half-life (intravenous (IV): 63.2 h; per os (PO): 46.9 h) with an acceptable ADME-Toxicity profile. When tested in Leishmania infected hamsters, no toxicity and limited efficacy were observed. Low solubility and degradation were investigated spectroscopically as possible causes for the sub-optimal pharmacokinetic properties. Compound 19 resulted a specific compound based on the screening against a protein set, following the intrinsic fluorescence changes. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Venkatesan; Maruthavanan, Asian Journal of Chemistry, 2011, vol. 23, # 5, p. 2121 - 2124
  作者：Venkatesan、Maruthavanan

  DOI：——

  日期：——