3-hydroxy-2-(1H-indol-3-yl)-6-methoxy-4H-chromen-4-one | 33268-72-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3-hydroxy-2-(1H-indol-3-yl)-6-methoxy-4H-chromen-4-one
• 英文别名: 3-hydroxy-2-indol-3-yl-6-methoxy-chromen-4-one；3-hydroxy-2-(1H-indol-3-yl)-6-methoxychromen-4-one
• CAS: 33268-72-3
• 化学式: C₁₈H₁₃NO₄
• 分子量: 307.306
• InChiKey: NTIFBHMAMRZNBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  71.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-hydroxy-2-(1H-indol-3-yl)-6-methoxy-4H-chromen-4-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以92%的产率得到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：

  1-(2'-hydroxy-5'-methoxyphenyl)-3-(1-indol-3-yl)-prop-2-en-1-one 在 sodium hydroxide 、 双氧水 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 3-hydroxy-2-(1H-indol-3-yl)-6-methoxy-4H-chromen-4-one
  参考文献：
  名称：

  Venturella; Bellino; Piozzi, Farmaco, Edizione Scientifica, 1971, vol. 26, # 7, p. 591 - 596

  摘要：

  DOI：