6-[4-(三氟甲氧基)苯基]-3-吡啶甲醛 | 851069-97-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 6-[4-(三氟甲氧基)苯基]-3-吡啶甲醛
• 英文名称: 6-(4-(trifluoromethoxy)phenyl)nicotinaldehyde
• 英文别名: 6-[4-(Trifluoromethoxy)phenyl]-3-pyridinecarbaldehyde；6-[4-(trifluoromethoxy)phenyl]pyridine-3-carbaldehyde
• CAS: 851069-97-1
• 化学式: C₁₃H₈F₃NO₂
• 分子量: 267.207
• InChiKey: NEKWUGFVJNIXIK-UHFFFAOYSA-N

物化性质

• 沸点：
  336.3±42.0 °C(Predicted)
• 密度：
  1.335±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-[4-(三氟甲氧基)苯基]-3-吡啶甲醛 在 对甲苯磺酸 、 pyridinium chlorochromate 作用下， 以 乙醚 、 二氯甲烷 、 正丁醇 为溶剂， 反应 25.0h， 生成 3-methyl-2-[6-[4-(trifluoromethoxy)phenyl]-3-pyridyl]-7-(trifluoromethyl)-1H-quinolin-4-one
  参考文献：
  名称：

  Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2)

  摘要：

  Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC50 = 15 nM PfNDH2; IC50 = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED50/ED90 of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.

  DOI：

  10.1021/jm201184h
• 作为产物：
  描述：

  2-溴-5-醛基吡啶 、 4-三氟甲氧基苯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 18.08h， 以71%的产率得到6-[4-(三氟甲氧基)苯基]-3-吡啶甲醛
  参考文献：
  名称：

  抗结核和抗寄生虫的2-硝基咪唑并吡嗪并酮具有增强的效力和溶解性

  摘要：

  在批准德拉曼尼德和苯曼尼曼尼德作为治疗抗药性结核病的新药之后，现在人们对双环硝基咪唑支架作为抵抗传染病的一种治疗方法有了新的兴趣。我们最近描述了具有有希望的抗结核和抗寄生虫活性的硝基咪唑并吡嗪酮双环亚类，促使人们付出更多的努力来产生具有改善的溶解度和增强的效力的类似物。通过（i）将极性官能团引入亚甲基接头，（ii）用较少的亲脂性杂环取代末端苯基，或（iii）产生延伸的联芳基侧链，对关键的侧基芳基取代基进行修饰。联芳基侧链具有更好的抗结核和抗胰体活性，大部分类似物的活性比单芳基母体化合物高2至175倍，并引入吡啶基时，其溶解度得到了令人鼓舞的改善。这项研究有助于理解硝基咪唑并吡嗪酮支架与一组致病生物的现有结构-活性关系（SAR），以支持未来的铅优化。

  DOI：

  10.1021/acs.jmedchem.0c01372

文献信息

• Indolyl and dihydroindolyl derivatives, their manufacture and use as pharmaceutical agents
  申请人：Ackermann Jean

  公开号：US20050096353A1

  公开（公告）日：2005-05-05

  This invention relates to compounds of the formula wherein one of R 6 , R 7 and R 8 is and X, Y 1 to Y 4 , R 1 to R 14 and n are as defined in the description, and to all enantiomers and pharmaceutically acceptable salts and/or esters thereof The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by PPARδ and/or PPARα agonists.

  这项发明涉及以下式的化合物 其中R 6 、R 7 和R 8 中的一个是 和X、Y 1 至Y 4 、R 1 至R 14 和n如描述中所定义的，并且所有的对映体和药用盐和/或酯。该发明还涉及含有这种化合物的药物组合物，以及用于制备它们的方法和它们用于治疗和/或预防由PPARδ和/或PPARα激动剂调节的疾病。
• [EN] CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS DE LA CÉRAMIDE GALACTOSYLTRANSFÉRASE POUR LE TRAITEMENT DE MALADIES
  申请人：BIOMARIN PHARM INC

  公开号：WO2019104011A1

  公开（公告）日：2019-05-31

  Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.

  本发明涉及化合物、制造此类化合物的方法、包含此类化合物的药物组合物和药剂，以及使用此类化合物治疗或预防与鞘氨醇半乳糖基转移酶（CGT）相关疾病或失调的方法，例如，例如，溶酶体贮积病。溶酶体贮积病的例子包括，例如，克拉伯病和异染性脑白质营养不良。
• Phenyl derivatives, their manufacture and use as pharmaceutical agents
  申请人：Ackermann Jean

  公开号：US20050096337A1

  公开（公告）日：2005-05-05

  This invention relates to compounds of the formula wherein one of R 5 , R 6 and R 7 is and X 1 , X 2 , Y 1 to Y 4 , R 1 to R 13 and m and n are defined in the description, and to all enantiomers and pharmaceutically acceptable salts and/or esters thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by PPARδ and/or PPARα agonists.

  这项发明涉及以下结构的化合物 其中R 5 、R 6 和R 7 中的一个是 以及X 1 、X 2 、Y 1 到Y 4 、R 1 到R 13 以及m和n在描述中有定义，以及所有的对映体和药用上可接受的盐和/或酯。该发明还涉及含有这类化合物的药物组合物，以及用于制备它们的方法以及它们用于治疗和/或预防由PPARδ和/或PPARα激动剂调节的疾病的用途。
• [EN] ANTIMALARIAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIPALUDIQUES
  申请人：LIVERPOOL SCHOOL TROPICAL MEDICINE

  公开号：WO2012069856A1

  公开（公告）日：2012-05-31

  The present invention relates to antimalarial compounds. More specifically, the present invention relates to novel substituted quinolone derivatives of formula (I) and related quinoline derivatives of formula (II) as defined herein that possess potent antimalarial activity. The present invention also relates to processes for the preparation of these quinolone and quinoline derivatives, to pharmaceutical compositions comprising them and to their use as therapeutic agents for the treatment and/or prevention of malaria.

  本发明涉及抗疟疾化合物。更具体地，本发明涉及具有强效抗疟活性的本发明中定义的新型取代喹诺酮衍生物（式（I））和相关喹啉衍生物（式（II））。本发明还涉及制备这些喹诺酮和喹啉衍生物的方法，包括含有它们的药物组合物以及它们作为治疗和/或预防疟疾的治疗剂的用途。
• 2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties
  作者：Sitthivut Charoensutthivarakul、W. David Hong、Suet C. Leung、Peter D. Gibbons、Paul T. P. Bedingfield、Gemma L. Nixon、Alexandre S. Lawrenson、Neil G. Berry、Stephen A. Ward、Giancarlo A. Biagini、Paul M. O'Neill

  DOI：10.1039/c5md00062a

  日期：——

  2-Pyridylquinolones with improved solubility, an improved metabolic stability profile, reduced off-target toxicity and 12 nM Plasmodium falciparum antimalarial activity are described.

  描述了具有改善溶解性、改善代谢稳定性、减少非靶标毒性和12 nM Plasmodium falciparum 抗疟活性的2-吡啶基喹啉类化合物。