3-(benzo[d][1,3]dioxol-5-yl)benzaldehyde | 1181320-63-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 3-(benzo[d][1,3]dioxol-5-yl)benzaldehyde
• 英文别名: 3-(Benzo[1,3]dioxol-5-yl)benzaldehyde；3-(1,3-benzodioxol-5-yl)benzaldehyde
• CAS: 1181320-63-7
• 化学式: C₁₄H₁₀O₃
• 分子量: 226.232
• InChiKey: SPTAXVKZXVZADL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  3-(benzo[d][1,3]dioxol-5-yl)benzaldehyde 在 双氧水 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 2-(3-(benzo[d][1,3]dioxol-5-yl)phenyl)-3-hydroxy-6-methoxy-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：

  间溴苯甲醛 、 3.4-(亚甲基二氧基)苯硼酸 在 5%-palladium/activated carbon 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以54%的产率得到3-(benzo[d][1,3]dioxol-5-yl)benzaldehyde
  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

文献信息

• Aryl thiosemicarbazones for the treatment of trypanosomatidic infections
  作者：Pasquale Linciano、Carolina B. Moraes、Laura M. Alcantara、Caio H. Franco、Bruno Pascoalino、Lucio H. Freitas-Junior、Sara Macedo、Nuno Santarem、Anabela Cordeiro-da-Silva、Sheraz Gul、Gesa Witt、Maria Kuzikov、Bernhard Ellinger、Stefania Ferrari、Rosaria Luciani、Antonio Quotadamo、Luca Costantino、Maria Paola Costi

  DOI：10.1016/j.ejmech.2018.01.043

  日期：2018.2

  interesting activity against the same organisms. The compounds were particularly effective against T. brucei and T. cruzi. Among the 28 synthesized compounds, the best one was (E)-2-(4-((3.4-dichlorobenzyl)oxy)benzylidene) hydrazinecarbothioamide (A14) yielding a comparable anti-parasitic activity against the three parasitic species (TbEC50 = 2.31 μM, LiEC50 = 6.14 μM, TcEC50 = 1.31 μM) and a Selectivity Index

  基于显示出抗锥虫病活性的噻二唑衍生物库，我们已经考虑了噻二唑的开放形式和反应中间体硫代半脲类化合物，作为针对布鲁氏锥虫（Tb），婴儿利什曼原虫（Li）和克氏锥虫（Tc）。相似的化合物已经显示出对相同生物的有趣活性。该化合物对T. brucei和T. cruzi特别有效。在这28种合成的化合物中，最好的一种是（E）-2-（4-（（3.4-二氯苄基）氧基）亚苄基）肼基甲硫代酰胺（A14）针对三种寄生物（Tb EC 50  = 2.31μM，Li EC 50  = 6.14μM，Tc EC 50  = 1.31μM ）产生可比的抗寄生虫活性，并且相对于人类巨噬细胞的选择性指数高于10，因此显示泛抗锥虫病活动。（E）-2-（（（3'.4'-二甲氧基-[1.1'-联苯] -3-基]甲基）甲基）肼基甲硫代酰胺（A12）和（E）-2-（4-（（3.4-二氯苄基）氧基）苯亚甲基）肼硫代甲酰胺（A14）在组
• 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.