5-(4-Fluorophenyl)-2-[(4-methylsulfinyl)benzylthio]-4-(4-pyridyl)imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-Fluorophenyl)-2-[(4-methylsulfinyl)benzylthio]-4-(4-pyridyl)imidazole
• 英文别名: 4-[5-(4-Fluorophenyl)-2-(4-methanesulfinyl-benzylsulfanyl)-3H-imidazol-4-yl]pyridine；4-[4-(4-fluorophenyl)-2-[(4-methylsulfinylphenyl)methylsulfanyl]-1H-imidazol-5-yl]pyridine
• 化学式: C₂₂H₁₈FN₃OS₂
• 分子量: 423.535
• InChiKey: PRYUWQSCZBKGMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-methylsulfinylbenzyl chloride 、 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydro-imidazole-2-thione 以 乙醇 为溶剂， 反应 4.0h， 以41%的产率得到5-(4-Fluorophenyl)-2-[(4-methylsulfinyl)benzylthio]-4-(4-pyridyl)imidazole
  参考文献：
  名称：

  From Imidazoles to Pyrimidines:  New Inhibitors of Cytokine Release

  摘要：

  On the basis of model imidazole inhibitors of cytokine release, a series of novel pyridinyl pyrimidine derivatives was prepared and tested on their ability to inhibit the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-beta) from peripheral blood mononuclear cells (PBMC) and human whole blood. In the pyrimidine series, structure-activity relationships (SARs) similar to those of the imidazole series were found, although generally pyrimidine compounds were less potent. Modification of the substituent at the 2 position of the pyrimidine led to the most active compound 14 which inhibited release of TNF-alpha (IC50 = 3.2 muM) and IL-1beta (IC50 = 2.3 muM) from PBMC as effectively as the model imidazole inhibitor ML 3163 (TNF-alpha, IC50 = 3.7 muM; IL-1beta, IC50 = 0-9 muM). Screening in an isolated enzyme assay revealed both imidazole and pyrimidine compounds as inhibitors of p38 MAP (mitogen-activated protein) kinase.

  DOI：

  10.1021/jm011098a

文献信息

• 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.
• 2-ARYLALKYLTHIO -IMIDAZOLE, 2-ARYLALKENYL -THIO -IMIDAZOLE UND 2-ARYLALKINYL -THIO -IMIDAZOLE ALS ENTZÜNDUNGS -HEMMSTOFFE UND HEMMSTOFFE DER CYTOKIN -FREISETZUNG
  申请人：MERCKLE GMBH

  公开号：EP1112265A1

  公开（公告）日：2001-07-04
• Transdiscal administration of inhibitors of p38 MAP kinase
  申请人：Brown Laura J.

  公开号：US20090162351A1

  公开（公告）日：2009-06-25

  The present invention relates to methods, formulations and kits for administering a p38 MAP kinase inhibitor or other therapeutic agent into an intervertebral disc, such as a diseased disc, for example, for purposes of prevention and treatment of degenerative and other disorders.
• Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints
  申请人：Brown Laura J.

  公开号：US20090162376A1

  公开（公告）日：2009-06-25

  The present invention relates to trans-capsularly administering into a diseased joint an inhibitor of p38 MAP kinase or a different therapeutic agent.
• US6432988B1
  申请人：——

  公开号：US6432988B1

  公开（公告）日：2002-08-13