3,4-二甲氧基联苯-3-甲醛 | 676348-36-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3,4-二甲氧基联苯-3-甲醛
• 英文名称: 3’,4’-dimethoxy-[1,1’-biphenyl]-3-carbaldehyde
• 英文别名: 3-(3,4-Dimethoxyphenyl)benzaldehyde
• CAS: 676348-36-0
• 化学式: C₁₅H₁₄O₃
• mdl: MFCD03424647
• 分子量: 242.274
• InChiKey: PEIHWSWXATULIX-UHFFFAOYSA-N

物化性质

• 沸点：
  382.0±37.0 °C(Predicted)
• 密度：
  1.130±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 安全说明：
  S26,S36/37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2922299090

反应信息

• 作为反应物：
  描述：

  3,4-二甲氧基联苯-3-甲醛 在 双氧水 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 2-(3’,4’-dimethoxy-[1,1’-biphenyl]-3-yl)-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 、 3,4-二甲氧基苯硼酸 在 5%-palladium/activated carbon 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以62%的产率得到3,4-二甲氧基联苯-3-甲醛
  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
• Substituted Aminopyridines and Uses Thereof
  申请人：Albert Jeffrey Scott

  公开号：US20080287399A1

  公开（公告）日：2008-11-20

  This invention relates to novel compounds having the structural formula (I) and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  本发明涉及具有结构式（I）的新化合物及其药学上可接受的盐、组合物和使用方法。这些新化合物可用于治疗或预防认知障碍、阿尔茨海默病、神经退行性疾病和痴呆症。
• Antibacterial Biaromatic Derivatives
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：US20160075722A1

  公开（公告）日：2016-03-17

  The invention relates to antibacterial compounds of formula I (I) wherein R is H, cyano, alkoxy, cyanomethoxy, cycloalkylmethoxy, hydroxyalkoxy, alkoxyalkoxy, alkoxycarbonyl, 2-ethoxy-2-oxoethoxy, 2-(methylamino)-2-oxoethoxy, (1-cyanocyclobutyl)methoxy, 3-hydroxy-pyrrolidin-1-yl or 3,4-dihydroxycyclopentyl)methoxy; U 1 is N or CR 1 , U 2 is N or CR 1 , U 3 is N or CR 3 and U 4 is N or CR 1 , it being understood that at most three of U 1 , U 2 , U 3 and U 4 can be N at the same time; V 1 is N or CR 5 , V 2 is N or CR 6 , V 3 is N or CR 7 and V 4 is N or CH, it being understood that at most two of V 1 , V 2 , V 3 and V4 can be N at the same time; R1 is H, cyano, hydroxy or alkoxy; R2 is H, hydroxy or alkoxy; R 3 is H, cyano, hydroxy, alkoxy or carboxamido; R 4 is H or alkoxy; R 5 is H, hydroxy or halogen; R 6 is H, hydroxy or halogen; R 7 is H; the dotted line “______” represents a bond or is absent; W represents CH or N when the dotted line “______” is a bond, or W represents CH 2 when the dotted line “______” is absent; X represents CH or N; and Q represents O or S; and salts thereof.

  本发明涉及式I的抗菌化合物（I），其中R为H，氰基，烷氧基，氰甲氧基，环烷基甲氧基，羟基烷氧基，烷氧基烷氧基，烷氧基羧酰基，2-乙氧基-2-氧代乙氧基，2-（甲基氨基）-2-氧代乙氧基，（1-氰基环丁基）甲氧基，3-羟基吡咯烷-1-基或3,4-二羟基环戊基）甲氧基；U1为N或CR1，U2为N或CR1，U3为N或CR3，U4为N或CR1，其中最多只能同时有三个U1，U2，U3和U4为N；V1为N或CR5，V2为N或CR6，V3为N或CR7，V4为N或CH，其中最多只能同时有两个V1，V2，V3和V4为N；R1为H，氰基，羟基或烷氧基；R2为H，羟基或烷氧基；R3为H，氰基，羟基，烷氧基或羧酰胺基；R4为H或烷氧基；R5为H，羟基或卤素；R6为H，羟基或卤素；R7为H；虚线“______”表示键或不存在；当虚线“______”为键时，W表示CH或N，当虚线“______”不存在时，W表示CH2；X表示CH或N；Q表示O或S；以及其盐。
• NOVEL BIPHENYL DERIVATIVE COMPOUND AND USE THEREOF
  申请人：Ewha University-Industry Collaboration Foundation

  公开号：EP3805193A1

  公开（公告）日：2021-04-14

  The present disclosure provides a novel biphenyl derivative compound, an optical isomer thereof or a pharmaceutically acceptable salt thereof. The biphenyl derivative compound, optical isomer thereof or pharmaceutically acceptable salt thereof according to the present disclosure may induce cancer cell death by damaging mitochondria and inducing ATP depletion in cells which are in a nutrient-starved state such as a glucose-starved state, which is the normal environment of cancer cells. In addition, it is an Nm23-H1/NDPK activity-increasing substance that may suppress cancer metastasis and growth. Thus, it exhibits excellent effects not only on the prevention, alleviation and treatment of cancer, but also on the suppression of cancer metastasis.

  本公开提供了一种新型联苯衍生物化合物、其光学异构体或其药学上可接受的盐。根据本公开的联苯衍生物化合物、其光学异构体或其药学上可接受的盐可通过破坏线粒体和诱导处于营养匮乏状态（如葡萄糖匮乏状态）的细胞（即癌细胞的正常环境）中的 ATP 耗竭来诱导癌细胞死亡。此外，它还是一种提高 Nm23-H1/NDPK 活性的物质，可抑制癌症的转移和生长。因此，它不仅在预防、缓解和治疗癌症方面有出色的效果，在抑制癌症转移方面也有出色的效果。
• EP3805193
  申请人：——

  公开号：——

  公开（公告）日：——