N-{4-[4-(4-fluorophenyl)-1-methyl-2-methylsulfanyl-1H-imidazol-5-yl]pyridin-2-yl}acetamide | 452056-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-{4-[4-(4-fluorophenyl)-1-methyl-2-methylsulfanyl-1H-imidazol-5-yl]pyridin-2-yl}acetamide
• 英文别名: CBS-3408；4-(4-Fluorophenyl)-1-methyl-5-(2-acetamido-4-pyridyl)-2-methylthioimidazole；N-[4-[5-(4-fluorophenyl)-3-methyl-2-methylsulfanylimidazol-4-yl]pyridin-2-yl]acetamide
• CAS: 452056-93-8
• 化学式: C₁₈H₁₇FN₄OS
• 分子量: 356.424
• InChiKey: CJKGORBZVWDVRY-UHFFFAOYSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  85.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{4-[4-(4-fluorophenyl)-1-methyl-2-methylsulfanyl-1H-imidazol-5-yl]pyridin-2-yl}acetamide 在 盐酸 、 水 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 14.0h， 以82%的产率得到4-(4-(4-fluorophenyl)-1-methyl-2-(methylthio)-1H-imidazol-5-yl)pyridin-2-amine
  参考文献：
  名称：

  Imidazole compounds having an antiinflammatory effect

  摘要：

  这项发明涉及公式I的2-磺酰基或2-磺酰基取代的咪唑衍生物， 其中基团R1、R2、R3和R4具有描述中指示的含义。该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功能障碍相关的疾病。

  公开号：

  EP1894925A1
• 作为产物：
  描述：

  2-(乙酰氨基)-4-甲基吡啶 在 4-二甲氨基吡啶 、 potassium permanganate 、 2,2,4,4-四甲基-1,3-环丁烷二硫酮 、 氢溴酸 、 sodium methylate 、 potassium carbonate 、 N,N'-羰基二咪唑 、 亚硝酸异戊酯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 70.25h， 生成 N-{4-[4-(4-fluorophenyl)-1-methyl-2-methylsulfanyl-1H-imidazol-5-yl]pyridin-2-yl}acetamide
  参考文献：
  名称：

  Identification of Regioisomers in a Series of N-Substituted Pyridin-4-yl Imidazole Derivatives by Regiospecific Synthesis, GC/MS, and ¹H NMR

  摘要：

  The regiospecific synthesis of 2a (Scheme 3), a novel and potent pyridinyl imidazole inhibitor of p38 MAP (mitogen-activated protein) kinase, and the regioselective preparation of its regioisomer 2b (Scheme 4) are described. Chromatographic and spectroscopic data are presented, which in this class of compounds allow the unambiguous identification of regioisomers prepared by a nonregiospecific synthetic strategy. Biological data demonstrating the importance of the correct regiochemistry for inhibition of p38 are given.

  DOI：

  10.1021/jo026619w

文献信息

• Novel Substituted Pyridinyl Imidazoles as Potent Anticytokine Agents with Low Activity against Hepatic Cytochrome P450 Enzymes
  作者：Stefan A. Laufer、Gerd K. Wagner、Dunja A. Kotschenreuther、W. Albrecht

  DOI：10.1021/jm030766k

  日期：2003.7.1

  been linked to the liver toxicity observed for model p38 inhibitors, was very efficiently reduced through introduction of a tetramethylpiperidine substituent at the 1 position of the imidazole nucleus. Combination of both structural features provided 14c (p38: 0.34 microM, inhibition of CYP1A2 0%, 2C9 2.6%, 2C19 7.6% at 10 microM), which was selected for further development.

  制备了一系列p38 MAP（有丝分裂原活化蛋白）激酶的多取代吡啶-4-基咪唑抑制剂，作为小分子抗细胞因子药物和候选药物，用于治疗慢性炎性疾病。评估了吡啶基和咪唑部分的取代基对选择性抑制p38的贡献，而没有伴随的细胞色素P450相互作用。将1-苯基乙基（7e，p38：IC（50）0.38 microM）或乙酰基取代基放置在几个2-氨基吡啶咪唑的环外氮原子上导致鉴定出有效的p38抑制剂，该抑制剂超过了起始铅ML 3375（p38：IC （50）0.63 microM）效能。初步的模型研究将7e的增强生物活性与其1-苯基乙基氨基侧链和靠近p38接头区域的疏水口袋之间的新型相互作用相关。该系列中最活跃的p38抑制剂在功能性PBMC（外周血单个核细胞）和全血测定中保持了其功效。此外，与在模型p38抑制剂中观察到的肝毒性有关的细胞色素P450相互作用，通过在咪唑核的1位上引入四甲基哌啶取代基而非常有效
• 2-thio-substituted imidazole derivatives and the use thereof in the pharmaceutical industry
  申请人：——

  公开号：US20040116416A1

  公开（公告）日：2004-06-17

  The invention relates to 2-thio-substituted imidazole derivatives of the formula I 1 in which the radicals R 1 , R 2 , R 3 and R 4 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I1中的2-硫代取代咪唑衍生物，其中基团R1，R2，R3和R4如描述中所定义。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。
• IMIDAZOLE COMPOUNDS HAVING AN ANTIINFLAMMATORY EFFECT
  申请人：Albrecht Wolfgang

  公开号：US20100069436A1

  公开（公告）日：2010-03-18

  The invention relates to imidazole derivatives of the Formula (I) in which the radicals R 1 , R 2 , R 3 , R 4 and R 5 have the meanings indicated in the description. The compounds of the invention have an immunomodulating and/or cytokine release-inhibiting effect and are therefore suitable for the treatment of disorders associated with an impairment of the immune system.

  本发明涉及式（I）的咪唑衍生物，其中基团R1、R2、R3、R4和R5具有说明书中指示的含义。该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受损有关的疾病。
• 2-SULFINYL- AND 2-SULFONYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS
  申请人：Albrecht Wolfgang

  公开号：US20100273833A1

  公开（公告）日：2010-10-28

  The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula (I) in which the radicals R 1 , R 2 , R 3 and R 4 have the meaning indicated in the description. The compounds of the invention have an immunomodulating and/or cytokine release-inhibiting effect and are therefore suitable for the treatment of disorders associated with an impairment of the immune system.

  本发明涉及式(I)的2-亚磺酰基或2-磺酰基取代的咪唑衍生物，其中基团R1、R2、R3和R4的含义如说明书所示。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损伤有关的疾病。
• Tri- and tetrasubstituted imidazoles as p38α mitogen-activated protein kinase inhibitors
  作者：Stefan Laufer、Dominik Hauser、Thomas Stegmiller、Claudia Bracht、Kathrin Ruff、Verena Schattel、Wolfgang Albrecht、Pierre Koch

  DOI：10.1016/j.bmcl.2010.09.012

  日期：2010.11

  The synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles as potent p38 alpha mitogen-activated protein kinase inhibitors is described. The trisubstituted imidazole series was found to be more potent than the tetrasubstituted imidazole series. Many of these compounds show low-nanomolar activities in the isolated p38 alpha MAP kinase inhibition assay. The structure-activity relationships between these two series are different and not comparable. (C) 2010 Elsevier Ltd. All rights reserved.