N-[3-methylthiophenyl-(tolylthio)methyl]formamide | 165806-89-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-[3-methylthiophenyl-(tolylthio)methyl]formamide
• 英文别名: N-[(4-methylphenyl)sulfanyl-(3-methylsulfanylphenyl)methyl]formamide
• CAS: 165806-89-3
• 化学式: C₁₆H₁₇NOS₂
• 分子量: 303.449
• InChiKey: ZOORXUBWFAJQBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[3-methylthiophenyl-(tolylthio)methyl]formamide 在 1,5,7-三氮杂双环[4.4.0]癸-5-烯 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 18.5h， 生成 1-[3-(4-Morpholinyl)propyl]-4-(3-methylthio phenyl)-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：

  4-甲苯硫酚 、 3-(甲基硫代)苯甲醛 、 formamide 以 甲苯 为溶剂， 反应 18.0h， 生成 N-[3-methylthiophenyl-(tolylthio)methyl]formamide
  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

• Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase
  作者：Timothy F. Gallagher、George L. Seibel、Shouki Kassis、Jeffrey T. Laydon、Mary Jane Blumenthal、John C. Lee、Dennis Lee、Jeffrey C. Boehm、Susan M. Fier-Thompson、Jeffrey W. Abt、Margaret E. Soreson、Juanita M. Smietana、Ralph F. Hall、Ravi S. Garigipati、Paul E. Bender、Karl F. Erhard、Arnold J. Krog、Glenn A. Hofmann、Peter L. Sheldrake、Peter C. McDonnell、Sanjay Kumar、Peter R. Young、Jerry L. Adams

  DOI：10.1016/s0968-0896(96)00212-x

  日期：1997.1

  Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC alpha and ERK kinase activity is observed. Copyright (C) 1997 Elsevier Science Ltd.