5,7-Difluoro-1H-benzo[D][1,3]oxazine-2,4-dione | 1196151-35-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 5,7-Difluoro-1H-benzo[D][1,3]oxazine-2,4-dione
• 英文别名: 5,7-difluoro-1H-3,1-benzoxazine-2,4-dione
• CAS: 1196151-35-5
• 化学式: C₈H₃F₂NO₃
• 分子量: 199.114
• InChiKey: SHRQGYVJMJFQRO-UHFFFAOYSA-N

物化性质

• 密度：
  1.596±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,7-Difluoro-1H-benzo[D][1,3]oxazine-2,4-dione 在 三氟甲磺酸 、 zinc(II) chloride 作用下， 以 氯苯 、 正丁醇 为溶剂， 反应 48.0h， 生成 (R)-1-(4-(5,7-difluoro-3-methyl-4-oxo-1,4-dihydroquinolin-2-yl)phenyl)-N,N-dimethylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis

  摘要：

  A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified similar to 100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further similar to 90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.

  DOI：

  10.1021/acs.jmedchem.6b01718
• 作为产物：
  描述：

  2-氨基-4,6-二氟苯甲酸 、 三光气 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 生成 5,7-Difluoro-1H-benzo[D][1,3]oxazine-2,4-dione
  参考文献：
  名称：

  [EN] TRYPTANTHRIN DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS DE TRYPTANTHRINE ET LEURS UTILISATIONS

  摘要：

  The present disclosure provides tryptanthrin derivatives that are modulators of IDO2 and pharmaceutical compositions comprising these compounds. The present disclosure further provides methods of using these compounds for the treatment of disease.

  公开号：

  WO2023211977A1

文献信息

• 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.
• Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of <i>Mycobacterium tuberculosis</i>
  作者：W. David Hong、Peter D. Gibbons、Suet C. Leung、Richard Amewu、Paul A. Stocks、Andrew Stachulski、Pedro Horta、Maria L. S. Cristiano、Alison E. Shone、Darren Moss、Alison Ardrey、Raman Sharma、Ashley J. Warman、Paul T. P. Bedingfield、Nicholas E. Fisher、Ghaith Aljayyoussi、Sally Mead、Maxine Caws、Neil G. Berry、Stephen A. Ward、Giancarlo A. Biagini、Paul M. O’Neill、Gemma L. Nixon

  DOI：10.1021/acs.jmedchem.6b01718

  日期：2017.5.11

  A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified similar to 100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further similar to 90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.
• [EN] TRYPTANTHRIN DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE TRYPTANTHRINE ET LEURS UTILISATIONS
  申请人：[en]VISCIENT BIO, INC.

  公开号：WO2023211977A1

  公开（公告）日：2023-11-02

  The present disclosure provides tryptanthrin derivatives that are modulators of IDO2 and pharmaceutical compositions comprising these compounds. The present disclosure further provides methods of using these compounds for the treatment of disease.