ML 3375

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ML 3375
• 英文别名: 4-[4-(4-fluorophenyl)-2-methylsulfanyl-1H-imidazol-5-yl]pyridine
• 化学式: C₁₅H₁₂FN₃S
• 分子量: 285.345
• InChiKey: IKQIPPKRAFLUKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-溴-4-甲基吡啶 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hexamethyldisilazane 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 160.0 ℃ 、101.33 kPa 条件下， 反应 10.5h， 生成 ML 3375
  参考文献：
  名称：

  A concise and optimized four-step approach toward 2-(aryl-)alkylsulfanyl-, 4(5)-aryl-, 5(4)-heteroaryl-substituted imidazoles using alkyl- or arylalkyl thiocyanates

  摘要：

  A convenient cyclization method leading to trisubstituted imidazoles in up to 84% yield is reported. Diverse 1-aryl-, 2heteroaryl-substituted ethanones are converted into the corresponding alpha-oximino derivatives which are reduced under regioselective conditions. The obtained alpha-amino carbonyl intermediates are reacted with alkyl- or arylalkyl thiocyanates to directly yield C(2)-S-substituted imidazole. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.07.147

文献信息

• [DE] 2-THIO-SUBSTITUIERTE IMIDAZOLDERIVATE UND IHRE VERWENDUNG IN DER PHARMAZIE<br/>[EN] 2-THIO-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE IN PHARMACEUTICS<br/>[FR] DERIVES D'IMIDAZOL 2-THIO-SUBSTITUES ET LEUR UTILISATION DANS LE DOMAINE PHARMACEUTIQUE
  申请人：MERCKLE GMBH

  公开号：WO2004018458A1

  公开（公告）日：2004-03-04

  Die Erfindung betrifft 2-Thio-substituierte Imidazolderivate der Formel (I) worin die Reste R1, R2, R3 und m die in der Beschreibung angegebene Bedeutung besitzen. Die erfindungsgemässen Verbindungen besitzen eine immunmodulierende und/oder die Cytokinfreisetzung hemmende Wirkung und sind daher geeignet zur Behandlung von Erkrankungen, die mit einer Störung des Immunsystems im Zusammenhang stehen.

  这项发明涉及式(I)的2-硫代取代咪唑衍生物，其中残基R1、R2、R3和m具有描述中所指定的含义。根据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相关的疾病。
• 2-Thio-substituted imidazole derivatives and their use in pharmaceutics
  申请人：Laufer Stefan

  公开号：US20060235054A1

  公开（公告）日：2006-10-19

  The invention relates to 2-thio-substituted imidazole derivatives of the formula I in which the radicals R 1 , R 2 R 3 and m 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和m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相关的疾病。
• 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-THIO-SUBSTITUIERTE IMIDAZOLDERIVATE UND IHRE VERWENDUNG IN DER PHARMAZIE
  申请人：MERCKLE GMBH

  公开号：EP1539741A1

  公开（公告）日：2005-06-15
• US7582660B2
  申请人：——

  公开号：US7582660B2

  公开（公告）日：2009-09-01