4-(4-fluorophenyl)-5-(2-(tetrahydro-2H-pyran-4-ylamino)pyridin-4-yl)-1,3-dihydroimidazol-2-thione | 1012305-59-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-fluorophenyl)-5-(2-(tetrahydro-2H-pyran-4-ylamino)pyridin-4-yl)-1,3-dihydroimidazol-2-thione
• 英文别名: 4-(4-Fluorophenyl)-5-[2-(oxan-4-ylamino)pyridin-4-yl]-1,3-dihydroimidazole-2-thione
• CAS: 1012305-59-7
• 化学式: C₁₉H₁₉FN₄OS
• 分子量: 370.45
• InChiKey: AANLDWFXWPXPJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  90.3
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-溴-1,2-并二酚 、 4-(4-fluorophenyl)-5-(2-(tetrahydro-2H-pyran-4-ylamino)pyridin-4-yl)-1,3-dihydroimidazol-2-thione 在 potassium tert-butylate 作用下， 以 甲醇 为溶剂， 反应 3.5h， 以31%的产率得到3-(4-(4-fluorophenyl)-5-(2-(tetrahydro-2H-pyran-4-ylamino)pyridin-4-yl)-1H-imidazol-2-ylthio)propane-1,2-diol
  参考文献：
  名称：

  Targeting the Ribose and Phosphate Binding Site of p38 Mitogen-Activated Protein (MAP) Kinase: Synthesis and Biological Testing of 2-Alkylsulfanyl-, 4(5)-Aryl-, 5(4)-Heteroaryl-Substituted Imidazoles

  摘要：

  Three series of substituted 2-alkylsulfanyl-4-(4-fluorophenyl)imidazoles, 5-pyridinyl-, 1-methyl-5-pyridinyl-, and 5-(2-aminopyridin-4-yl)-imidazoles, were prepared and tested for their ability to inhibit p38 MAP kinase and TNF-alpha release. These compounds were prepared by using different synthetic routes. They were tested by applying a nonradioactive p38 MAP kinase assay and by measurement of TNF-a release in human whole blood. Potent inhibitors (IC(50)values in the low nanomolar range, as low as 2 nM in the enzyme assay and 37 nM in the human whole blood test) were identified by variation of substituents at the imidazole-C2-thio position as well as at the 2-aminopyridinyl functionality. In contrast to other known kinase inhibitors, these novel imidazole derivatives with the substituents at the imidazole-C2-thio position may interact with the ribose as well as with the phosphate binding site of the p38 MAP kinase.

  DOI：

  10.1021/jm800373t
• 作为产物：
  描述：

  2-amino-1-(4-fluorophenyl)-2-(2-(tetrahydro-2H-pyran-4-ylamino)pyridin-4-yl)ethanone hydrochloride 、 potassium thioacyanate 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-(4-fluorophenyl)-5-(2-(tetrahydro-2H-pyran-4-ylamino)pyridin-4-yl)-1,3-dihydroimidazol-2-thione
  参考文献：
  名称：

  对新型4（5）-芳基-5（4）-杂芳基-2-硫代取代的咪唑的合成及其p38 MAP激酶抑制活性的改进。

  摘要：

  制备了一系列的2-烷基硫烷基-4-（4-氟苯基）-5-（2-氨基吡啶-4-基）取代的咪唑，并且将2-硫醚部分与p38 MAP激酶的磷酸/核糖结合口袋相互作用的可能性被调查了。通过亲核取代或通过钯催化的芳基-CN-键形成在吡啶部分引入烷基/苄基氨基官能团。

  DOI：

  10.1039/b717605h

文献信息

• KINASE MODULATORS FOR THE TREATMENT OF CANCER
  申请人：Synovo GmbH

  公开号：US20170313661A1

  公开（公告）日：2017-11-02

  A method of treating cancer in which a compound that inhibits the expression, production or release of IL-10 by immune cells is combined with a compound that stimulates the production of IL-12 when given in combination with, or in the presence of TNFa. Said method is effective when provided in addition to standard therapies, notably chemotherapy using cytotoxic drugs and other forms of immune therapy including therapeutic vaccines.

  一种治疗癌症的方法，其中抑制免疫细胞表达、产生或释放IL-10的化合物与在与TNFa联合给予或存在的情况下刺激IL-12产生的化合物结合。所述方法在提供标准疗法的基础上有效，特别是包括使用细胞毒性药物的化疗和其他形式的免疫疗法，包括治疗性疫苗。
• 2-SULFANYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS
  申请人：Burnet Michael

  公开号：US20090270462A1

  公开（公告）日：2009-10-29

  The invention relates to 2-thio-substituted imidazole derivatives of the Formula I, and to methods of use thereof.

  这项发明涉及到式I的2-硫代咪唑衍生物，以及其使用方法。
• US8143294B2
  申请人：——

  公开号：US8143294B2

  公开（公告）日：2012-03-27
• US9617221B2
  申请人：——

  公开号：US9617221B2

  公开（公告）日：2017-04-11
• [EN] KINASE MODULATORS FOR THE TREATMENT OF CANCER<br/>[FR] MODULATEURS DE KINASE POUR LE TRAITEMENT DU CANCER
  申请人：SYNOVO GMBH

  公开号：WO2011100769A2

  公开（公告）日：2011-08-18

  A method of treating cancer in which a compound that inhibits the expression, production or release of IL-IO by immune cells is combined with a compound that stimulates the production of IL- 12 when given in combination with, or in the presence of TNFa. Said method is effective when provided in addition to standard therapies, notably chemotherapy using cytotoxic drugs and other forms of immune therapy including therapeutic vaccines.