6-methoxy-3-methyl-2-(6-(4-(trifluoromethoxy)phenyl)pyridin-3-yl)quinolin-4(1H)-one | 1361967-06-7

• 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
• 英文名称: 6-methoxy-3-methyl-2-(6-(4-(trifluoromethoxy)phenyl)pyridin-3-yl)quinolin-4(1H)-one
• 英文别名: 6-methoxy-3-methyl-2-[6-[4-(trifluoromethoxy)phenyl]-3-pyridyl]-1H-quinolin-4-one；6-methoxy-3-methyl-2-[6-[4-(trifluoromethoxy)phenyl]pyridin-3-yl]-1H-quinolin-4-one
• CAS: 1361967-06-7
• 化学式: C₂₃H₁₇F₃N₂O₃
• 分子量: 426.395
• InChiKey: KDCZGJWDVFWONV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-methoxy-3-methyl-2-(6-(4-(trifluoromethoxy)phenyl)pyridin-3-yl)quinolin-4(1H)-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以10%的产率得到6-hydroxy-3-methyl-2-(6-(4-(trifluoromethoxy)phenyl)pyridin-3-yl)quinolin-4(1H)-one
  参考文献：
  名称：

  2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties

  摘要：

  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。

  DOI：

  10.1039/c5md00062a
• 作为产物：
  描述：

  2-溴-5-醛基吡啶 在 四(三苯基膦)钯 、 三氟甲磺酸 、 potassium carbonate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 正丁醇 为溶剂， 反应 27.0h， 生成 6-methoxy-3-methyl-2-(6-(4-(trifluoromethoxy)phenyl)pyridin-3-yl)quinolin-4(1H)-one
  参考文献：
  名称：

  2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties

  摘要：

  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。

  DOI：

  10.1039/c5md00062a

文献信息

• [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。
• Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting <i>Plasmodium falciparum</i> Type II NADH:Quinone Oxidoreductase (PfNDH2)
  作者：Suet C. Leung、Peter Gibbons、Richard Amewu、Gemma L. Nixon、Chandrakala Pidathala、W. David Hong、Bénédicte Pacorel、Neil G. Berry、Raman Sharma、Paul A. Stocks、Abhishek Srivastava、Alison E. Shone、Sitthivut Charoensutthivarakul、Lee Taylor、Olivier Berger、Alison Mbekeani、Alasdair Hill、Nicholas E. Fisher、Ashley J. Warman、Giancarlo A. Biagini、Stephen A. Ward、Paul M. O’Neill

  DOI：10.1021/jm201184h

  日期：2012.3.8

  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.
• 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。