1-(4-fluorophenyl)-2-(pyridin-4-yl)hydroximido-ethan-2-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluorophenyl)-2-(pyridin-4-yl)hydroximido-ethan-2-one
• 英文别名: 1-(4-fluorophenyl)-2-pyridin-4-ylethane-1,2-dione 1-oxime；2-(4-fluorophenyl)-1-(pyridin-4-yl)ethan-1,2-dione-2-oxime；1-(4-Fluoro-phenyl)-2-pyridin-4-yl-ethane-1,2-dione1-oxime；2-(4-fluorophenyl)-2-hydroxyimino-1-pyridin-4-ylethanone
• 化学式: C₁₃H₉FN₂O₂
• 分子量: 244.225
• InChiKey: CEOAQNUWZZZBMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-2-(pyridin-4-yl)hydroximido-ethan-2-one 在 2,2,4,4-四甲基-1,3-环丁烷二硫酮 作用下， 生成 4-(4-fluorophenyl)-1-methyl-5-(pyridin-4-yl)-1H-imidazole-2-thione
  参考文献：
  名称：

  Ones, Thiones, andN-Oxides: An Exercise in Imidazole Chemistry

  摘要：

  DOI：

  10.1002/1521-3773(20020703)41:13<2290::aid-anie2290>3.0.co;2-r
• 作为产物：
  描述：

  2-(4-氟-苯基)-1-吡啶-4-乙酮 、 sodium nitrite 在 ice 、 title compound 、 水 、 四磷十氧化物 作用下， 以 溶剂黄146 、 水 为溶剂， 反应 3.0h， 生成 1-(4-fluorophenyl)-2-(pyridin-4-yl)hydroximido-ethan-2-one
  参考文献：
  名称：

  2-Thio-substituted imidazole derivatives and their use in pharmaceutics

  摘要：

  本发明涉及公式I中的2-硫代取代咪唑衍生物，其中基团R1，R2，R3，R4和p如描述中所定义。本发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统紊乱有关的疾病。

  公开号：

  US20060252810A1

文献信息

• Macrocyclic compounds and methods of use thereof
  申请人：Synovo GmbH

  公开号：US07767797B1

  公开（公告）日：2010-08-03

  The invention features novel macrocyclic compounds, methods of making the compounds, pharmaceutical compositions including the compounds, and methods of treatment using the compounds.

  这项发明涉及新颖的大环化合物，制备这些化合物的方法，包括这些化合物的药物组合物，以及使用这些化合物进行治疗的方法。
• Heteroaryl-cyclic acetals
  申请人：Collis Alan

  公开号：US20050090501A1

  公开（公告）日：2005-04-28

  Compounds of formula (I) are described in which Het is a five or six membered heteroaromatic ring of the formula in which one of R 1 and R 2 is optionally substituted heteroaryl and the other is optionally substituted heteroaryl or optionally substituted aryl; X 1 is a bond, X 3 and X 4 are each independently N or C and X 2 and X 5 are independently CH, N, NH, O or S; or X 3 and X 4 are C, one of X 1 , X 2 and X 5 is N and the others are N or CH; but excluding compounds in which X 1 is a bond, one of X 2 and X 5 is N and the other is NH and X 3 and X 4 are both C; R 3 represents a group -L 1 -R 6 ; R 4 represents hydrogen, alkyl or hydroxyalkyl; or R 3 and R 4 , when attached to the same carbon atom, may form with the said carbon atom a cycloalkyl, cycloalkenyl or heterocycloalkyl ring or a group C═CH 2 ; R 5 represents hydrogen or alkyl; and m is zero or an integer 1 or 2; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates of compounds of formula (I) and N-oxides thereof, and their prodrugs. The compounds are TNF inhibitors and are useful as pharmaceuticals.

  描述了式(I)化合物，其中Het是式的五元或六元杂环芳香环：其中R1和R2中的一个是可选取代的杂芳基，另一个是可选取代的杂芳基或可选取代的芳基；X1是键，X3和X4分别独立地是N或C，X2和X5独立地是CH、N、NH、O或S；或者X3和X4是C，X1、X2和X5中的一个是N，其他是N或CH；但不包括其中X1是键，X2和X5中的一个是N，另一个是NH，X3和X4都是C的化合物；R3表示一个-L1-R6基团；R4表示氢、烷基或羟基烷基；或者当附加到同一个碳原子时，R3和R4可以与所述碳原子形成环状烷基、环状烯基或杂环烷基环或C═CH2基团；R5表示氢或烷基；m为零或整数1或2；以及其N-氧化物和其前药；化合物的式(I)和其N-氧化物的药学上可接受的盐和溶剂；这些化合物是TNF抑制剂，可用于制药。
• 2-Thio-substituted imidazole derivatives and their use in pharmaceutics
  申请人：Laufer Stefan

  公开号：US20060252810A1

  公开（公告）日：2006-11-09

  The invention relates to 2-thio-substituted imidazole derivatives of the formula I in which the radicals R 1 , R 2 , R 3 , R 4 and p are as defined in the description. The compounds according to the invention have immunomodulating and/or cytokine-release-inhibiting action and are therefore suitable for treating disorders associated with a disturbed immune system.

  本发明涉及公式I中的2-硫代取代咪唑衍生物，其中基团R1，R2，R3，R4和p如描述中所定义。本发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统紊乱有关的疾病。
• Targeting the Ribose and Phosphate Binding Site of p38 Mitogen-Activated Protein (MAP) Kinase: Synthesis and Biological Testing of 2-Alkylsulfanyl-, 4(5)-Aryl-, 5(4)-Heteroaryl-Substituted Imidazoles
  作者：Pierre Koch、Christiane Bäuerlein、Hartmut Jank、Stefan Laufer

  DOI：10.1021/jm800373t

  日期：2008.9.25

  Three series of substituted 2-alkylsulfanyl-4-(4-fluorophenyl)imidazoles, 5-pyridinyl-, 1-methyl-5-pyridinyl-, and 5-(2-aminopyridin-4-yl)-imidazoles, were prepared and tested for their ability to inhibit p38 MAP kinase and TNF-alpha release. These compounds were prepared by using different synthetic routes. They were tested by applying a nonradioactive p38 MAP kinase assay and by measurement of TNF-a release in human whole blood. Potent inhibitors (IC(50)values in the low nanomolar range, as low as 2 nM in the enzyme assay and 37 nM in the human whole blood test) were identified by variation of substituents at the imidazole-C2-thio position as well as at the 2-aminopyridinyl functionality. In contrast to other known kinase inhibitors, these novel imidazole derivatives with the substituents at the imidazole-C2-thio position may interact with the ribose as well as with the phosphate binding site of the p38 MAP kinase.
• Imidazole Inhibitors of Cytokine Release:  Probing Substituents in the 2 Position
  作者：Stefan A. Laufer、Hans-Günther Striegel、Gerd K. Wagner

  DOI：10.1021/jm020873z

  日期：2002.10.1

  Novel 2,4,5-trisubstituted imidazole derivatives were prepared as potential anticytokine agents. Thirty-seven compounds were tested on their ability to inhibit the release of tumor necrosis factor-a (TNF-alpha and interleukin-1beta (IL-beta) from peripheral blood mononuclear cells (PBMC) or human whole blood. SARs (structure activity relationships) for substituents-at the 4 and 5 position of the imidazole core were similar to those described for other inhibitors of cytokine. release and p38 MAP (mitogen-activated protein) kinase. Starting from benzylsulfanyl imidazole 2b (IC50 p(38), 4.0 muM; TNF-alpha, 1.1,muM; IL-1beta, 0.38,muM), the contribution of substituents at the 2 Position to enzyme inhibitory and cellular activity of test compounds was investigated. This strategy led to the identification of compound 2q (IC50 p38, 0.63 muM; TNF-alpha, 0.90 muM; IL-1beta, 0.04,muM), which was 6-10 times more potent than the initial lead 2b with respect to inhibition of p38 and IL-1beta release and equipotently inhibited TNF-alpha release.