4-fluorophenyltolylsulfonomethylisocyanide | 165806-85-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-fluorophenyltolylsulfonomethylisocyanide
• 英文别名: 4'-fluorophenyl-(tolylthio)methylisocyanide；1-Fluoro-4-[isocyano-(4-methylphenyl)sulfanylmethyl]benzene
• CAS: 165806-85-9
• 化学式: C₁₅H₁₂FNS
• 分子量: 257.331
• InChiKey: FSFYWIRRJYTBII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  29.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-fluorophenyltolylsulfonomethylisocyanide 在 dipotassium peroxodisulfate 、 1,5,7-三氮杂双环[4.4.0]癸-5-烯 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 1-[2-(Methylsulfinyl)phenyl]-4-(4-fluorophenyl)-5-(pyridin-4-yl)imidazole
  参考文献：
  名称：

  1-Substituted 4-Aryl-5-pyridinylimidazoles:  A New Class of Cytokine Suppressive Drugs with Low 5-Lipoxygenase and Cyclooxygenase Inhibitory Potency

  摘要：

  A series of 1-alkyl- or -aryl-4-aryl-5-pyridinylimidazoles (A) were prepared and tested for their ability to bind to a recently discovered protein kinase termed CSBP and to inhibit lipopolysaccharide (LPS)-stimulated TNF production in mice. The kinase, CSBP, appears to be involved in a signaling cascade initiated by a number of inflammatory stimuli and leading to the biosynthesis of the inflammatory cytokines IL-1 and TNF. Two related imidazole classes (B and C) had previously been reported to bind to CSBP and to inhibit LPS-stimulated human monocyte IL-1 and TNF production. The members of the earlier series exhibited varying degrees of potency as inhibitors of the enzymes of arachidonic acid metabolism, PGHS-1 and 5-LO. Several of the more potent CSBP ligands and TNF biosynthesis inhibitors among the present series of N-1-alkylated imidazoles (A) were tested as inhibitors of PGHS-1 and 5-LO and were found to be weak to inactive as inhibitors of these enzymes. One of the compounds, 9 (SE 210313) which lacked measureable activity as an inhibitor of the enzymes of arachidonate metabolism, and had good potency in the binding and in vivo TNF inhibition assays, was tested for antiarthritic activity in the AA rat model of arthritis. Compound 9 significantly reduced edema and increased bone mineral density in this model.

  DOI：

  10.1021/jm960415o
• 作为产物：
  描述：

  N-[(4-fluorophenyl)-(4-methylphenyl)sulfanylmethyl]formamide 在 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 以53%的产率得到4-fluorophenyltolylsulfonomethylisocyanide
  参考文献：
  名称：

  1-Substituted 4-Aryl-5-pyridinylimidazoles:  A New Class of Cytokine Suppressive Drugs with Low 5-Lipoxygenase and Cyclooxygenase Inhibitory Potency

  摘要：

  A series of 1-alkyl- or -aryl-4-aryl-5-pyridinylimidazoles (A) were prepared and tested for their ability to bind to a recently discovered protein kinase termed CSBP and to inhibit lipopolysaccharide (LPS)-stimulated TNF production in mice. The kinase, CSBP, appears to be involved in a signaling cascade initiated by a number of inflammatory stimuli and leading to the biosynthesis of the inflammatory cytokines IL-1 and TNF. Two related imidazole classes (B and C) had previously been reported to bind to CSBP and to inhibit LPS-stimulated human monocyte IL-1 and TNF production. The members of the earlier series exhibited varying degrees of potency as inhibitors of the enzymes of arachidonic acid metabolism, PGHS-1 and 5-LO. Several of the more potent CSBP ligands and TNF biosynthesis inhibitors among the present series of N-1-alkylated imidazoles (A) were tested as inhibitors of PGHS-1 and 5-LO and were found to be weak to inactive as inhibitors of these enzymes. One of the compounds, 9 (SE 210313) which lacked measureable activity as an inhibitor of the enzymes of arachidonate metabolism, and had good potency in the binding and in vivo TNF inhibition assays, was tested for antiarthritic activity in the AA rat model of arthritis. Compound 9 significantly reduced edema and increased bone mineral density in this model.

  DOI：

  10.1021/jm960415o

文献信息

• Imidazole compounds, use and process of making
  申请人：——

  公开号：US05593991A1

  公开（公告）日：1997-01-14

  Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.

  小说1,4,5-取代咪唑化合物和用于治疗的组合物，作为细胞因子抑制剂。
• Compounds
  申请人：SmithKline Beecham Corporation

  公开号：US05593992A1

  公开（公告）日：1997-01-14

  Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.

  1,4,5-取代咪唑化合物及其在治疗中作为细胞因子抑制剂使用的组合物。
• Oxazoles for treating cytokine mediated diseases
  申请人：SmithKline Beecham Corporation

  公开号：US06288062B1

  公开（公告）日：2001-09-11

  This invention relates to the novel oxazole compounds of Formula (I) and novel pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable diluent or carrier. This invention also relates to a method of inhibiting cytokines and the treatment of cytokine mediated diseases, in mammals, thereby by administration of an effective amount of a compound according to Formula (I).

  这项发明涉及到式（I）的新型噁唑化合物以及包括式（I）化合物和药用可接受的稀释剂或载体的新型药物组合物。该发明还涉及一种通过给哺乳动物按照式（I）的化合物的有效量进行给药来抑制细胞因子和治疗细胞因子介导疾病的方法。
• compounds of heteroaryl substituted imidazole, their pharmaceutical compositons and uses
  申请人：SmithKline Beecham Corporation

  公开号：US06335340B1

  公开（公告）日：2002-01-01

  Compounds of 1,4,5-substituted imidazole wherein one of the substituents can be a substituted pyrimidine, pyridazine or 1,2,4-triazine. These compounds and their pharmaceutical compositions are used in treating cytokine mediated diseases by inhibiting the production of IL-1 (interleukin-1), IL-8 (interleukin-8), and TNF (tumor necrosis factor).

  1,4,5-取代咪唑化合物，其中一个取代基可以是取代嘧啶、吡啶并[2,3-d]二嗪或1,2,4-三嗪。这些化合物及其药物组合物用于通过抑制IL-1（白细胞介素-1）、IL-8（白细胞介素-8）和TNF（肿瘤坏死因子）的产生来治疗细胞因子介导的疾病。
• Pyridyl-oxazoles and their use as cytokines inhibitors
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1306377A2

  公开（公告）日：2003-05-02

  This invention relates to the novel oxazole compounds of Formula (I) and novel pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable diluent or carrier. This invention also relates to a method of inhibiting cytokines and the treatment of cytokine mediated diseases, in mammals, thereby by administration of an effective amount of a compound according to Formula (I).

  本发明涉及式(I)的新型噁唑化合物和由式(I)化合物和药学上可接受的稀释剂或载体组成的新型药物组合物。 本发明还涉及一种抑制细胞因子和治疗细胞因子介导的疾病的方法，该方法通过在哺乳动物体内施用有效量的根据式（I）的化合物来实现。